Syphilis is an indolent systemic spirochetal infection that remains a global health concern. Increased rates of HIV infection and intravenous drug abuse have slowed attempts to eliminate syphilis. Although the incidence of syphilis is currently declining in the United States, it remains an important health concern for women. As women are often affected by syphilis during their reproductive years, the potential risks to offspring are great. Treponema pallidum, the etiologic agent of syphilis, readily traverses the placenta, resulting in fetal infection. Vertical transmission may occur at any gestational age and at any stage of syphilis. Congenital syphilis is a serious infection with profound effects on the fetus/neonate. Clearly, access to prenatal care is an important factor in prevention of this condition. In spite of the plethora of antibiotics presently available in our medical armamentarium, penicillin remains the only safe and effective agent for the treatment of syphilis in pregnancy. Penicillin desensitization is indicated in patients with proven penicillin allergy. Clearly, additional research to improve our prevention, diagnostic, and treatment strategies is needed as we move into the new millennium, to further reduce the morbidity and mortality associated with syphilis and congenital syphilis. Copyright (C) 2000 Elsevier Science Inc.