Genital herpes simplex virus infection is a recurrent, lifelong disease with no cure. The strongest predictor for infection is a person's number of lifetime sex partners. The natural history includes first-episode mucocutaneous infection, establishment of latency in the dorsal root ganglion, and subsequent reactivation. Most infections are transmitted via asymptomatic viral shedding. Classic outbreaks consist of a skin prodrome and possible constitutional symptoms such as headache, fever, and inguinal lymphadenopathy. As the infection progresses, papules, vesicles on an erythematous base, and erosions appear over hours to days. These lesions usually crust, re-epithelialize, and heal without scarring. First-episode infections are more extensive: primary lesions last two to six weeks versus approximately one week for lesions in recurrent disease. Atypical manifestations are common. Infected persons experience a median of four recurrences per year after their first episode, but rates vary greatly. Genital herpes simplex virus type 2 recurs six times more frequently than type 1. Viral culture is preferred over polymerase chain reaction testing for diagnosis. Serologic testing can be useful in persons with a questionable history. Effective oral antiviral medications are available for initial, episodic, and suppressive therapy but are not a cure. There is some evidence that alternative therapies such as L-lysine, zinc, and some herbal preparations may offer some benefit. Counseling patients about the risk of transmission is crucial and helps prevent the spread of disease and neonatal complications.