Herpes simplex virus and varicella-zoster virus are common infections and are seen frequently in clinical practice. Infection with these viruses results in cutaneous lesions that may be diagnosed clinically, but widely available laboratory testing is useful for confirmation. Asymptomatic herpes simplex virus shedding, or "subclinical reactivation," likely occurs in all persons infected with herpes simplex virus and results in the transmission of virus despite the absence of signs or symptoms that suggest active infection. Oral and intravenous acyclovir are effective in treating initial and recurrent herpes simplex and varicella-zoster virus infections. The daily administration of oral acyclovir as suppressive therapy is effective in patients with frequently recurring genital infection with herpes simplex virus by reducing the number of symptomatic recurrences and the frequency of asymptomatic virus shedding. Two new antiviral agents, famciclovir and valacyclovir hydrochloride, have been approved for the short-term treatment of recurrent genital herpes simplex virus and recurrent zoster in nonimmunocompromised hosts. Famciclovir and valacyclovir demonstrate superior pharmacokinetics compared with acyclovir and allow for less frequent daily dosing with higher achievable serum drug concentrations. The attenuated live varicella virus vaccine is now available in the United States and prevents primary varicella-zoster virus infection in susceptible children and adults.