The Five Second Rule (a.k.a. FSR or 5SR) is a term used to describe the mechanics of casting and spirit based mana regeneration.
Every time a spell that uses mana is cast the caster will not receive any Spirit based mana regen for five seconds. Each time a spell is cast, it will refresh this five second period. However, certain talents can allow you to bypass this restriction. Druids can use Intensity, Priests can use Meditation and Mages can use Arcane Meditation.
On the character sheet, this is designated under the Spells dropdown beside "Mana Regen:". Mana regen "while casting" is used when inside the Five Second Rule. Mana regen "while not casting" is used when outside the Five Second Rule.
The Five Second Rule applies only to spells that consume mana. Spells that do not consume mana do not start the five second countdown. Some examples of zero mana spells include: