Human viruses known to be spread by sexual contact include herpes simplex viruses (HSV), papillomaviruses (HPV), human immunodeficiency virus (HIV), hepatitis B virus, and cytomegalovirus. Infections with the first three (HSV, HPV, and HIV) have reached epidemic proportions and pose global health concerns. Most of what we know about these human pathogens has been learned only recently, owing to the advent of DNA technologies and advances in culture techniques. In fact, our awareness of one virally transmitted venereal disease, acquired immunodeficiency syndrome, dates to the early 1980s. This paper touches on various aspects of the biology, pathogenesis, clinical manifestations, and, where applicable, oncogenicity of these agents, as well as current treatments and vaccine initiatives.