In the last half of the 20(th) century, medicine has made tremendous inroads against syphilis chiefly owing to the introduction of penicillin and vigorous public health initiatives. Yet, the world continues to be burdened by this disease. Since 2000, overall rates of syphilis have risen in the US and throughout the world. Furthermore, through its association with an increased risk of HIV infection, syphilis has acquired a new potential for morbidity and mortality. The aim of this review is to survey the latest knowledge about syphilis, including pathogenesis and host response, clinical manifestations, diagnostic methods and, especially, treatment and follow-up.