Rune Words can be made in Expansion games by placing runes in the sockets of an item (helm, body armor, weapon or shield), but only when all the following conditions are met:
- Low, normal or superior quality socketed item (excluding Wirt's Leg)
- Correct item type
- Exact number of sockets
- Enabled patch (Single Player and Other Multiplayer) and game mode (some are Ladder only)
- Correct runes
- Runes placed in correct order
Since runes cannot be recovered once they have been placed in sockets, proceed with caution.
Six failed attempts to make an Insight polearm
(from left to right, top to bottom): incorrect item quality; incorrect item type; too many sockets; not made in a Ladder game; incorrect rune; incorrect order.
Rune Words can benefit from the modifiers of up to 6 runes, and can have up to 7 modifiers of their own, which can make them extremely powerful (particularly when made in Elite armor and weapons). It is best to repair an item before using it to make a Rune Word, since the cost can increase significantly once rune and Rune Word modifiers have been added (particularly if the item is superior, or has its own skill bonuses).
Rune Words can also be made in ethereal items for increased base defense or damage and decreased requirements and durability, although they cannot be repaired or recharged. This is only recommended when they are to be used by a mercenary (since it will not lose durability), or they are Indestructible (Breath of the Dying, Death, Eternity or Oath weapon) or Repair Durability (Exile auric shield or Prudence body armor).
Ethereal normal armor socketed using the Horadric Cube applies the ethereal defense bonus a second time: for example, normal Sacred Armor has (487-600) base defense so ethereal Sacred Armor has (730-900), but after socketing it will have (1,095-1,350). This can be (ab)used to create Rune Word armor with extremely high defense: for example, a Prudence body armor's (140-170)% Enhanced Defense would result in (2,628-3,645) defense when made in the socketed ethereal Sacred Armor.
Since Rune Words can have variable modifiers, in the event of an unfavorable roll the Horadric Cube can also be used to remove the Rune Word for another attempt. Although the runes will be destroyed, they can sometimes be much more easily replaced than the armor or weapon: for example, the runes needed for the Spirit Rune Word are very common but a Sacred Targe (Paladin Only) with All Resistances +45 is much rarer.
All 78 enabled Rune Words are listed alphabetically in the table below, although they can also be sorted by number of sockets, patch, Ladder and minimum required level.
- Those enabled for Battle.net in 1.07 were not enabled for Single Player and other Multiplayer until 1.09.
- Duress, Prudence, Splendor and Wind were enabled for Battle.net in 1.10, but were not enabled for SP and other MP until 1.11.
- Ladder Rune Words are only enabled for Ladder realm games on closed Battle.net: they are not enabled for SP and other MP unless the Rune Word Mod has been downloaded and correctly installed. Once a season ends, any Ladder Rune Words made during that season can still be used by normal (non-Ladder) realm characters.
- Minimum required level is normally the highest rlvl of any rune used, although final rlvl is the highest rlvl of the base item and any rune used. Holy Thunder has minimum rlvl 24 due to its +3 Holy Shock (Paladin Only) skill bonus (Holy Shock has rlvl 24). 
- Armor Upgrade Defense Calculator or Weapon Upgrade Damage Calculator can be used to view completed Rune Word armor or weapon stats (excluding durability).
- All 78 LoD rune words are available in all Expansion game modes in Resurrected. Ladder-only LoD rune words can be created in non-ladder Expansion games in D2R.