Spell and Ability Resists
Every time you use a spell or ability on an enemy, such as a Mage's Frostbolt or a Priest's Psychic Scream, there is a chance that it will be resisted. When resisted, an enemy either completely negates (fully resists) or partially negates (partially resists) the attack. The level of your enemy in relation to yours is one of the main factors governing resists. Enemies of higher level than yours have a higher chance to resist your spells and abilities.
Inherent resistances, such as fire resistance, will increase the chance that spells of that type will be resisted. However, having more of certain character attributes such as Spell Penetration will reduce your target's resistances, lowering the chance that your spells are resisted.