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.