You can obtain runes by killing Bosses, completing quests or from other tasks. To use the rune, drag it and place it on the desired item.
Note: Runes are divided in 3 tiers of rarity,  Common, Uncommon and Rare.

Flaming : Every 2 to 4 attacks sets enemies on fire for 1.00 to 2.50 seconds.

Frozen : Gives enemies Slowness I to IV for 1.00 to 2.50 seconds.

Venemous : Every 1 to 4 attacks gives enemies Poison I to III for 1.00 to 2.50 seconds.

Sharp : Increases melee damage by 0.50 to 2.00.

Heavy : [Axe Only] Increases knockback by 10.0% to 50.0%.

Hooked: [Sword Only] Reverses knockback and modifies to 30.0% to 80.0%.

Of Death : Every 2 to 5 attacks gives enemies Wither I to II for 1.00 to 4.00 seconds.

Of Mending : Passively regenerates durability over time) Note : 1 durability per 5 seconds when held.

Of Slaying : Increases melee damage against mobs by 1.00 to 8.00.