Publisher Summary Treponema pallidum subsp. pallidum is the causative agent of syphilis, a sexually transmitted infection (STI), with diverse clinical manifestations that occur in distinct stages. Just as many emerging infectious diseases, syphilis is at first highly virulent, but over time it becomes a more chronic infection. Regardless of its origin, syphilis spread across the world in the sixteenth century aided by human migrations associated with commerce and conflicts. Despite the advent of effective antibiotic therapies in the mid-twentieth century, syphilis continues to be a worldwide public health problem, particularly because of its association with infection by human immunodeficiency virus (HIV). The emergence of the HIV epidemic has re-emphasized the importance of syphilis as a health problem. Control of syphilis is currently based on sex education with promotion of condom use, diagnostic screening for blood donors, pregnant women, military recruits, high-risk groups, treatment of infected individuals, and partner notification and treatment.