Antiviral agents play a key role in the prevention and treatment of varicella zoster virus (VZV) disease in immunosuppressed patients. Randomized trials show that aciclovir is effective in preventing VZV reactivation disease; however, no consensus exists on dose, duration and patient population for its use. The recent shortage of VZV-specific immunoglobulin has generated renewed interest in the use of antiviral agents as post-exposure prophylaxis. The use of antiviral agents for post-exposure prophylaxis is not supported by randomized trials, but uncontrolled experience suggests that it might be a reasonable alternative if varicella-specific immunoglobulin is not available. Current evidence on the use of antiviral agents in the prevention of reactivation disease and management of exposure to VZV is discussed.