Mucocutaneous lesions are by far the most common manifestation of herpes simplex virus (HSV) infection. Genital herpes infection is one of the most important and common sexually transmitted diseases throughout the world. Our knowledge of HSV infections has increased dramatically since the initial historical descriptions of the clinical manifestations and histopathology of HSV lesions. Advances in our understanding of the natural history and pathogenesis of HSV infections have been paralleled by the development of both sensitive and specific tests that distinguish HSV-1 from HSV-2 infections and antiviral drugs that are selective inhibitors of viral replication. Type-specific serological markers of infection have allowed for a detailed evaluation of the epidemiology of infection. Establishing the unequivocal value of antiviral therapy has permitted clinicians to alter the spectrum of human disease and has implications for long-range control of HSV infections. The current level of biomedical knowledge sets the stage for application of the tools of molecular biology to the evaluation of human HSV disease, the evaluation of genetically engineered vaccines, and the development of antiviral therapeutics designed to be effective against newly identified virus-specific molecular targets [1-3]. These are practical future goals that should be achievable. This chapter summarizes the current status of our knowledge of the epide-Work performed and reported by the author was supported by Contract N0-1-AI-65306 from the Division of Virology of the National Institute of Allergy and Infectious Diseases, a grant from the Division of Research Resources (RR-032) from the National Institutes of Health, and a grant from the state of Alabama.