Rickettsial disease has recently undergone an important evolution, particularly in the field of molecular genetics. This development includes Mediterranean spotted fever (MSF), a tick-borne disease caused by Rickettsia conorii. Important changes have occurred in ecologic and epidemiologic comprehension of the disease, and in the occurrence of severe forms. However, many questions still remain, including the identity of the real vector and reservoir of R conorii, and whether other risk factors exist for a severe form of MSF.