Oral acyclovir is the treatment of choice for most patients with first episode genital herpes (Table 2). Therapy of first episode herpes may not be indicated in patients whose symptoms and lesions are clearly resolving at the time of presentation, and intravenous acyclovir therapy should be considered in patients with first episode herpes who require hospitalization. A viral culture should be obtained prior to initiating treatment in persons with first episode genital herpes, and typing should be performed to predict the risk and frequency of subsequent recurrences. Serologic differentiation of primary and nonprimary first episode disease is generally not performed outside the research setting. Suppression of recurrent genital herpes infections with daily oral acyclovir therapy has been shown to be safe and effective when continued for periods for up to 2 years. Oral acyclovir suppression should be considered in patients with frequent recurrences who complain of significant morbidity in association with their genital herpes infections (Table 2). The clinical benefit from episodic treatment of recurrent genital herpes infections is less dramatic. Patient-initiated therapy with oral acyclovir at the first sign of prodome or lesions should be considered in patients with relatively severe recurrences who are not candidates for suppressive treatment. Virologic confirmation of infection is encouraged. Oral acyclovir is the treatment of choice for short-term or long-term suppression in immunocompromised hosts, although short-term suppression with intravenous acyclovir may be indicated for persons who cannot take oral medications. Episodic treatment with topical, oral, and intravenous acyclovir is effective in immunocompromised patients, but topical treatment should be limited to persons with external lesions only.