Genital herpes simplex virus infection is the commonest cause of genital ulcerations in persons in industrialized nations. Overlap in the clinical manifestations of genital herpes with other infectious and noninfectious causes of genital ulcerations often requires clinicians to seek laboratory confirmation of the cause of a genital ulcer. The sensitivity of any laboratory procedure for detecting herpes simplex virus infection differs with the stage of the disease. Isolation of the herpes simplex virus in tissue culture is the most sensitive and specific laboratory test for the confirmation of genital herpes; cytologic and antigen detection techniques are approximately 50% and 70% as sensitive as viral isolation. The antiviral compound acyclovir is the first medication useful for the management of persons with genital herpes. Prevention of transmission of infection and recurrences of disease, however, has not been achieved. Description of the clinical manifestations of disease, its variable recurrence rate, and potential for future infectivity are issues that physicians should discuss with patients who have genital herpes.