Reactivation of the varicella-zoster virus (VZV) causes dermatomal herpes zoster (HZ) and more rarely severe disseminated HZ including diffuse rash, encephalitis, hepatitis, and pneumonitis. An atypical form of VZV infection, disseminated HZ has been described primarily in immunocompromised hosts. We report 2 cases of atypical disseminated HZ in immunocompromised patients presenting with diffuse, nondermatomal, vesicular eruptions. We also provide a review of the literature and summarize the current guidelines for the treatment and prophylaxis of HZ in patients with human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT), and hematopoietic stem cell transplantation (HSCT). Given the atypical presentation of VZV infection among some immunocompromised patients, this case series emphasizes the need for clinical suspicion for disseminated HZ to facilitate timely diagnosis and initiation of antiviral therapy. Clinician awareness of methods for prevention and treatment of VZV infection in immunocompromised individuals also is critical to minimize the risk for disease and associated morbidity in these patients.