The Best Rune Words - Diablo 2
This page contains a list of all the best Rune Words in Diablo 2 as well as a little bit of information about why they're on this list to begin with. Every Rune Word on this list is meant for characters who are level 50+, if you'd like to check out my other lists of Rune Words then follow the links below.
List of Armor Rune Words
List of Helm Rune Words
List of Shield Rune Words
List of Weapon Rune Words
List of Intermediate Rune Words
Runeword: Spirit
TalThulOrtAmn
Required Runes: 
Tal -- 
Thul -- 
Ort -- 
Amn
Level Req: 25
Other Req: Ladder Only
Slots: Shields and Swords
Both
+2 To All Skills
+25-35% Faster Cast Rate (varies)
+55% Faster Hit Recovery
+250 Defense Vs. Missile
+22 To Vitality
+89-112 To Mana (varies)
+3-8 Magic Absorb (varies)
Shields
Cold Resist +35%
Lightning Resist +35%
Poison Resist +35%
Attacker Takes Damage of 14
Swords
Adds 1-50 Lightning Damage
Adds 3-14 Cold Damage (3 Sec,Normal)
+75 Poison Damage Over 5 Seconds
7% Life Stolen Per Hit
Specifically the Spirit Shield Rune Word is the one that is "the best". There are plenty of better Rune Words that you can use for a weapon but Spirit offers you +2 to Skills on a shield which is very rare. Despite this being a level 25 Rune Word you can't typically use it until level 54+ when your character can equip a Monarch shield. Prior to the Monarch shield there are not many shields with 4 Sockets.
Runeword: Insight
RalTirTalSol
Required Runes: 
Ral -- 
Tir -- Tal -- 
Sol
Level Req: 27
Other Req: Ladder Only
Slots: Polearms & Staves
Level 12-17 Meditation Aura When Equipped (varies)
+35% Faster Cast Rate
+200-260% Enhanced Damage (varies)
+9 To Minimum Damage
180-250% Bonus to Attack Rating (varies)
Adds 5-30 Fire Damage
+75 Poison Damage Over 5 Seconds
+1-6 To Critical Strike (varies)
+5 To All Attributes
+2 To Mana After Each Kill
23% Better Chance of Getting Magic Items
This weapon makes every Rune Word list whether it be beginner, intermediate or the best Rune Words in the game. The reason for this is because Insight comes with Meditation Aura which gives you insanely good mana regeneration. When put into a Polearm and equipped onto an Act 2 Mercenary you'll share the Meditation Aura with him. Extra tip: Use an Ethereal Polearm as it can't break when your Mercenary is using it, you'll be able to boost his damage this way!
Runeword: Heart of the Oak
KoVexPulThul
Required Runes: 
Ko -- 
Vex -- 
Pul -- Thul
Level Req: 55
Other Req: N/A
Slots: Staves & Maces
+3 To All Skills
+40% Faster Cast Rate
+75% Damage To Demons
+100 To Attack Rating Against Demons
Adds 3-14 Cold Damage
7% Mana Stolen Per Hit
+10 To Dexterity
Replenish Life +20
Increase Maximum Mana 15%
All Resistances +30-40 (varies)
Level 4 Oak Sage (25 Charges)
Level 14 Raven (60 Charges)
Without a doubt this is the best universal caster Rune Word in the game. No matter what class you are this weapon will be useful to you as a Caster. I strongly recommend this Rune Word for any Casters who need a good weapon. Heart of the Oak, Chains of Honor and Sanctuary are a combination of Rune Words that I use on most of my Casters.
Runeword: Silence
DolEldHelIstTirVex
Required Runes: 
Dol -- 
Eld -- 
Hel -- 
Ist -- Tir -- Vex
Level Req: 55
Other Req: N/A
Slots: All Weapons
+2 to All Skills
+20% Increased Attack Speed
+20% Faster Hit Recovery
+200% Enhanced Damage
+75% Damage To Undead
+50 to Attack Rating Against Undead
11% Mana Stolen Per Hit
Hit Blinds Target +33
Hit Causes Monster to Flee 25%
All Resistances +75
+2 to Mana After Each Kill
30% Better Chance of Getting Magic Items
Requirements -20%
This Rune Word is popular as a Mercenary weapon, especially for Bowzons as it blinds monsters and causes them to flee which allows you to keep a distance on them. It also offers the Mercenary very high All Resist which will (obviously) help keep them alive on Hell.
Runeword: Death
HelElVexOrtGul
Required Runes: Hel -- 
El -- Vex -- Ort -- 
Gul
Level Req: 55
Other Req: Ladder Only
Slots: Swords & Axes
Indestructible
100% Chance To Cast Level 44 Chain Lightning When You Die
25% Chance To Cast Level 18 Glacial Spike On Attack
+300-385% Enhanced Damage (varies)
20% Bonus To Attack Rating
+50 To Attack Rating
Adds 1-50 Lightning Damage
7% Mana Stolen Per Hit
50% Chance of Crushing Blow
(0.5*Clvl)% Deadly Strike (Based on Character Level)
+1 To Light Radius
Level 22 Blood Golem (15 Charges)
Requirements -20%
This is one of the lowest level end game Rune Words which can be put into Ethereal weapons due to it making the item Indestructible. While there are some better Rune Words available you can't use them until you're a higher level.
Runeword: Chaos
FalOhmUm
Required Runes: 
Fal -- 
Ohm -- 
Um
Level Req: 57
Other Req: N/A
Slots: Claws Only
9% Chance To Cast Level 11 Frozen Orb On Striking
11% Chance To Cast Level 9 Charged Bolt On Striking
+35% Increased Attacked Speed
+240-290% Enhanced Damage (varies)
Adds 216-471 Magic Damage
25% Chance of Open Wounds
+1 To Whirlwind
+10 To Strength
+15 Life After Each Demon Kill
There is a whole Assassin spec built around this Rune Word and the Whirlwind attack that it provides called WWsin.
Runeword: Call to Arms
AmnRalMalIstOhm
Required Runes: Amn -- Ral -- 
Mal -- Ist -- Ohm
Level Req: 57
Other Req: N/A
Slots: All Weapons
+1 To All Skills
+40% Increased Attack Speed
+240-290% Enhanced Damage (varies)
Adds 5-30 Fire Damage
7% Life Stolen Per Hit
+2-6 To Battle Command (varies)
+1-6 To Battle Orders (varies)
+1-4 To Battle Cry (varies)
Prevent Monster Heal
Replenish Life +12
30% Better Chance of Getting Magic Items
This weapon is what's known as a Switch Weapon since it provides the player with Battle Command and Battle Orders. Both of these abilities last for a couple minutes (if you have a lot of + Skills and you roll high ranks on the weapon itself) and they boost your total Health, Mana and Stamina as well as your Skill Levels.
Basically, you keep this weapon equipped in your off hand and occasionally switch to it, buff yourself and then switch back.
Runeword: Fortitude
ElSolDolLo
Required Runes: El -- Sol -- Dol -- 
Lo
Level Req: 59
Other Req: Ladder Only
Slots: Weapons & Chest Armor
Both
20% Chance To Cast Level 15 Chilling Armor when Struck
+25% Faster Cast Rate
+300% Enhanced Damage
+200% Enhanced Defense
+((8-12)*0.125*Clvl) To Life (Based on Character Level) (varies)
All Resistances +25-30 (varies)
12% Damage Taken Goes To Mana
+1 To Light Radius
Weapons
+9 To Minimum Damage
+50 To Attack Rating
20% Deadly Strike
Hit Causes Monster To Flee 25%
Armor
+15 Defense
Replenish Life +7
+5% To Maximum Lightning Resist
Damage Reduced By 7
Fortitude Rune Word as a Chest Armor is one of the best melee armors available due to the fact that it offers Enhanced Damage on a piece of armor. Keep in mind that how Enhanced Damage is calculated on a piece of armor is different than on a weapon; for more information about that check out my link to the Fortitude page above.
Runeword: Beast
BerTirUmMalLum
Required Runes: 
Ber -- Tir -- Um -- Mal -- 
Lum
Level Req: 63
Other Req: N/A
Slots: Axes, Hammers & Scepters
Level 9 Fanaticism Aura When Equipped
+40% Increased Attack Speed
+240-270% Enhanced Damage (varies)
20% Chance of Crushing Blow
25% Chance of Open Wounds
+3 To Werebear
+3 To Lycanthropy
Prevent Monster Heal
+25-40 To Strength (varies)
+10 To Energy
+2 To Mana After Each Kill
Level 13 Summon Grizzly (5 Charges)
This weapon is best in slot for Summoner Necromancers since it grants all of your minions Fanaticism Aura which greatly boosts their damage.
Runeword: Infinity
BerMalBerIst
Required Runes: Ber -- Mal -- Ber -- Ist
Level Req: 63
Other Req: Ladder Only
Slots: Polearms Only
50% Chance To Cast Level 20 Chain Lightning When You Kill An Enemy
Level 12 Conviction Aura When Equipped
+35% Faster Run/Walk
+255-325% Enhanced Damage (varies)
-(45-55)% To Enemy Lightning Resistance (varies)
40% Chance of Crushing Blow
Prevent Monster Heal
+(0.5*Clvl) To Vitality (Based on Character Level)
30% Better Chance of Getting Magic Items
Level 21 Cyclone Armor (30 Charges)
Many Casters use this weapon on their mercenary because of the Conviction Aura that it comes with. Not only will this lower the Resists of all enemies you face but it also can break some Immunities that you encounter. Some builds that use primarily Lightning damage may use this on their character instead of their Mercenary for the -% to Enemy Lightning Resistance.
Runeword: Chains of Honor
DolUmBerIst
Required Runes: Dol -- Um -- Ber -- Ist
Level Req: 63
Other Req: N/A
Slots: Chest Armor
+2 To All Skills
+200% Damage To Demons
+100% Damage To Undead
8% Life Stolen Per Hit
+70% Enhanced Defense
+20 To Strength
Replenish Life +7
All Resistances +65
Damage Reduced By 8%
25% Better Chance of Getting Magic Items
This is the best universal chest armor in the entire game. It's useful for Casters, Melee and everything inbetween and is generally best in slot for many builds.
Runeword: Enigma
JahIthBer
Required Runes: 
Jah -- 
Ith -- Ber
Level Req: 65
Other Req: N/A
Slots: Chest Armor
+2 To All Skills
+45% Faster Run/Walk
+1 To Teleport
+750-775 Defense (Varies)
+(0.75*Clvl) To Strength (Based On Character Level)
Increase Maximum Life 5%
Damage Reduced By 8%
+14 Life After Each Kill
15% Damage Taken Goes To Mana
(1*Clvl)% Better Chance of Getting Magic Items (Based On Character Level)
Enigma is used by many classes and builds because of the fact that it provides Teleport to classes that are not Sorceress'. Aside from Chains of Honor this is probably one of the most popular Chest Armor Rune Words in the entire game.
Runeword: Dream
IoJahPul
Required Runes: 
Io -- Jah -- Pul
Level Req: 65
Other Req: Ladder Only
Slots: Helm and Shields
Both
10% Chance To Cast Level 15 Confuse When Struck
Level 15 Holy Shock Aura When Equipped
+20-30% Faster Hit Recovery (varies)
+30% Enhanced Defense
+150-220 Defense (varies)
+10 To Vitality
+(0.625*Clvl) To Mana (Based On Character Level)
All Resistances +5-20 (varies)
12-25% Better Chance of Getting Magic Items (varies)
Headgear
Increase Maximum Life 5%
Shields
+50 To Life
Dream is a great Rune Word to use in your Helm prior to finding something better. Many builds use items like Andariel's Visage or Griffon's Eye Diadem as their Helm, Dream is a good substitute until you can find one of these Best in Slot items.
Runeword: Ice
AmnShaelJahLo
Required Runes: Amn -- 
Shael -- Jah -- Lo
Level Req: 65
Other Req: Ladder Only
Slots: Missile Weapons (Bow & Crossbow)
100% Chance To Cast Level 40 Blizzard When You Level-up
25% Chance To Cast Level 22 Frost Nova On Striking
Level 18 Holy Freeze Aura When Equipped
+20% Increased Attack Speed
+140-210% Enhanced Damage (varies)
Ignore Target's Defense
+25-30% To Cold Skill Damage (varies)
7% Life Stolen Per Hit
-20% To Enemy Cold Resistance
20% Deadly Strike
(3.125*Clvl)% Extra Gold From Monsters (Based on Character Level)
For Bowzons who primarily use Freezing and Cold Arrow this is by far the best available weapon Rune Word. Thanks to the +% Cold Skill Damage and -% to Enemy Cold Resist it's difficult to find anything better for a Cold Bowzon.
Runeword: Faith
OhmJahLemEld
Required Runes: Ohm -- Jah -- 
Lem -- Eld
Level Req: 65
Other Req: Ladder Only
Slots: Missile Weapons (Bow & Crossbow)
Level 12-15 Fanaticism Aura When Equipped (varies)
+1-2 To All Skills (varies)
+330% Enhanced Damage
Ignore Target's Defense
300% Bonus To Attack Rating
+75% Damage To Undead
+50 To Attack Rating Against Undead
+120 Fire Damage
All Resistances +15
10% Reanimate As: Returned
75% Extra Gold From Monsters
Bowzons who don't use Ice Rune Word typically will use Faith instead. Fanaticism Aura is a big boost in DPS and the Reanimated As: Returned serves as both extra damage as well as giving you tanks to keep enemies away from you as you blast away from a distance.
Runeword: Last Wish
JahMalJahSurJahBer
Required Runes: Jah -- Mal -- Jah -- 
Sur -- Jah -- Ber
Level Req: 65
Other Req: Ladder Only
Slots: Axes, Hammers & Swords
6% Chance To Cast Level 11 Fade When Struck
10% Chance To Cast Level 18 Life Tap On Striking
20% Chance To Cast Level 20 Charged Bolt On Attack
Level 17 Might Aura When Equipped
+330-375% Enhanced Damage (varies)
Ignore Target's Defense
60-70% Chance of Crushing Blow (varies)
Prevent Monster Heal
Hit Blinds Target
(0.5*Clvl)% Chance of Getting Magic Items (Based on Character Level)
Many high end melee builds use the Last Wish Rune Word since it offers 60 - 70% Crushing Blow along with many other very nice bonuses.
Runeword: Breath of the Dying
VexHelElEldZodEth
Required Runes: Vex -- Hel -- El -- Eld -- 
Zod -- 
Eth
Level Req: 69
Other Req: N/A
Slots: All Weapons
50% Chance To Cast Level 20 Poison Nova When You Kill An Enemy
Indestructible
+60% Increased Attack Speed
+350-400% Enhanced Damage (varies)
-25% Target Defense
+50 To Attack Rating
+200% Damage To Undead
+50 To Attack Rating Against Undead
7% Mana Stolen Per Hit
12-15% Life Stolen Per Hit (varies)
Prevent Monster Heal
+30 To All Attributes
+1 To Light Radius
Requirements -20%
Breath of the Dying is the highest level Rune Word in the game and it is one of the few Rune Words which can be placed into an Ethereal weapon and used by the player without worrying about it breaking. Since this Rune Word makes the item Indestructible you don't have to worry about it breaking when you use it.