Inflammasomes are large intracellular complexes that induce inflammation in response to exogenous and endogenous damage signals. They regulate production and release of the proinflammatory cytokines IL-1β and IL-18, playing a defensive role against infections. Inflammasomes have also been involved in the pathogenesis of a wide range of autoinflammatory conditions that are caused by dysregulation of the IL-1 pathway, such as cryopyrinopathies and hereditary periodic fever syndromes. On top of that, research in recent years suggests that defects in inflammasome regulation and signaling associate with a number of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and others. In this review, we describe the inflammasome and mechanisms that trigger it, provide a brief review of autoinflammatory disorders and discuss the current understanding and emerging data from experimental and clinical studies for the role of the innate immune system and inflammasomes in the biology and pathogenesis of systemic autoimmune diseases.