Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome and characterized by recurrent episodes of fever, serositis, arthritis, dermal manifestations, and long-term renal complications. The MEFV gene was described in 1997 as the gene responsible for FMF and is inherited in autosomal recessive manner. It encodes mutated protein pyrin, an important player in the innate immune system and the component of inflammasome which leads to exaggerated inflammatory response through uncontrolled production of interleukin-1. The recent progress in molecular genetics and understanding of pathogenesis showed a more complicated picture of FMF inheritance, penetrance, and pathogenesis. The pathogenesis is not completely understood although the gene responsible for FMF has been identified. Whether the pyrin mutation effect in FMF is due to a loss of function or a gain of function is still controversial. The diagnosis is mainly clinical and the genetic testing is indicated to support it. Colchicine remains the mainstay of treatment of FMF since 1972. It decreases the attacks, improves quality of life, and prevents amyloidosis. The recent advances in genetic testing and molecular studies has led to the development of new therapies of interleukin-1 inhibitors; anakinra, canakinumab, and rilonacept.