Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic approaches. Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene. Pathogenesis is poorly understood. The clinical severity is in part related to the mutations involved. Tumour necrosis factor receptor-1-associated periodic syndrome (TRAPS) is caused by mutations in the TNFRSF1A gene. This results in decreased serum levels soluble TNF-receptor leading to inflammation due to unopposed TNF-alpha action. Results of treatment with recombinant TNF-receptor analogues are promising. The hyper IgD periodic fever syndrome (HIDS) is caused by mutations in the MVK gene, leading to mevalonate kinase deficiency. The pathogenesis remains unclear. Muckle-Wells syndrome (MWS) and familial cold urticaria (FCU) are probably allelic disorders. The gene has been located, but not identified.