Varicella-zoster virus (VZV) causes 2 clinical illnesses, varicella (chickenpox) and herpes zoster (shingles). The purpose of this review is to describe the role of antiviral therapy in the treatment of VZV infections in healthy and immunocompromised children. Acyclovir is the drug of choice for varicella and herpes zoster. The route of administration may be intravenous or oral, depending on the immunocompetence of the host. The clinical impact of acyclovir therapy is related directly to its use early in the clinical course and to the likely susceptibility of the patient to severe or life-threatening VZV infection. Patients who have the most clinical benefit are otherwise healthy adolescents with varicella infection and high-risk populations of immunocompromised children who have varicella or herpes zoster. The morbidity and mortality of VZV infections are reduced substantially by initiating acyclovir treatment early in the course of the disease.