The responses of acute inflammation and fever are protective responses triggered by infection of tissue damage, acting through the innate immune system. The study of a collection of disorders termed familial periodic fever syndromes has contributed to our understanding of the physiological processes underlying the homeostasis of inflammation and fever. These inherited disorders are characterized by recurrent episodes of fever and systemic inflammation. These conditions are not associated with autoantibody production or self-reactive T-cell responses. They are collectively called autoinflamatory syndromes. Unraveling the pathophysiology of these disorders has given rise to the concept that these conditions are due to an innate immune system that is either oversensitive and prone to activation by minor stimuli or is poorly regulated.