Genital herpes simplex infection is a common and troublesome condition that is more often due to herpes simplex type II virus than to type I virus. The first step in management is accurate diagnosis by virus culture or antigen recognition. General management involves explaining the natural history to the patient, giving advice on sexual behavior, contact tracing, and hygiene. Oral or intravenous acyclovir provides the most useful therapy for first attacks. Acyclovir cream has a similar effect with external lesions in mild attacks. A course of acyclovir, however, has no effect on subsequent recurrence. Recurrent attacks, being brief compared with first attacks, are less influenced by acyclovir therapy, which should be given early for maximal effect. Oral and intravenous therapy are effective in the treatment of genital and anal herpes simplex infection in patients with acquired immune deficiency syndrome. When oral therapy is used, doses may need to be increased. Acyclovir therapy is a valuable development compared with previously available antivirals for genital herpes simplex infection.