Abstract: Successful treatment of venereal syphilis using penicillin has been accepted practice since 1943. Yet, despite the fact that the causative organism is known, and that treatment is both inexpensive and readily available, syphilis continues to generate a heavy burden of morbidity and mortality. Of the 12 million cases of syphilis occurring worldwide, 2 million are in pregnant women: the resultant congenital syphilis kills more than 1 million babies each year. In developing economies, syphilis is largely endemic; and major economic and societal hurdles exist for increasing women’s access to appropriate antenatal testing and care. Developed economies have also seen a rapid increase in syphilis infections during the past 20 years, particularly among women of childbearing age. The historical stigma associated with syphilis means that it has not attracted the same funding and public awareness as other sexually transmitted infections such as human immunodeficiency virus. These factors, along with poor antenatal screening coverage among urban and ethnic populations, have combined to generate a situation where an epidemic of congenital syphilis, not seen since the 1950s, may occur. This review briefly revises the microbiology and clinical features of congenital syphilis and looks at the current prevalence and screening programs in developing and developed economies, using the current situation in the United Kingdom as an example. The current antenatal and infant treatment recommendations are presented, and consideration is given toward future challenges in preventing an epidemic of congenital syphilis.