Herpes zoster infections are more common and often more complicated in immunocompromised patients. The key clinical objective in these patients is to reduce the incidence of cutaneous and visceral dissemination that can lead to life-threatening complications. This is best achieved with prompt antiviral therapy, which should be instituted in all immunosuppressed zoster patients if presentation occurs within 1 week of rash onset or any time before full crusting of lesions. For localized disease, most patients can be treated with oral valaciclovir, famciclovir or aciclovir, with close outpatient follow-up. Intravenous aciclovir therapy is reserved for those with disseminated varicella zoster virus infection, ophthalmic involvement, very severe immunosuppression or the inability to take oral medications. Foscarnet is the drug of choice to treat aciclovir-resistant herpes zoster. Appropriate analgesic therapy should be combined with early antiviral treatment to reduce the incidence and severity of acute zoster pain and post-herpetic neuralgia.