Syphilis is a chronic disease with a waxing and waning course, the manifestations of which have been described for centuries. It occurs worldwide, and the incidence varies significantly with geographic location. Transmission is mainly by sexual contact. The causative organism, Treponema pallidum, was first described in 1905, but because of the inability to culture the organism and the limitations of direct microscopy, serologic testing is the mainstay of laboratory diagnosis. The disease has been arbitrarily divided into several stages. The primary stage is defined by a chancre at the site of inoculation. The secondary stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic manifestations. A variable asymptomatic latent period follows, which for epidemiologic purposes is divided into early (<1 year) and late (>1 year) stages. The early stages (primary, secondary, and early latent) are potentially infectious. The tertiary stage is the most destructive and is marked by cardiovascular and neurologic sequelae and gummatous involvement of any organ system. Congenital infection may result in protean early or late manifestations. Unlike many other bacteria causing infectious diseases, the organism remains sensitive to penicillin, and this remains the mainstay of therapy.