Syphilis is a systemic disease caused by the spirochete Treponema pallidum. The name of this ancient but pervasive infection is proverbial to health care providers. The worldwide recognition of this term, however, argues with the intricacy of the disease in addition to the diagnostic and therapeutic challenges that persistently affect the global control of syphilis up to the present. This article focuses on the varied presentations of the infection, earning the title the "great imitator." The article also tackles other significant concerns regarding this malady.