Primary care providers and hospitalists frequently encounter older or immunocompromised patients with herpes zoster accompanied by debilitating pain. Atypical presentations and zosteriform herpes simplex may present diagnostic challenges to clinicians. This article summarizes the background, evidence, and guidelines for the diagnosis, complications, treatment, and prevention of herpes zoster. Diagnosis of challenging cases relies on polymerase chain reaction as the preferred test. Treatment focuses on optimal use of antiviral therapy and analgesics. Prevention emphasizes utilization of a new recombinant zoster vaccine, which reduces the incidence of herpes zoster by more than 90% and is preferred to the live attenuated herpes zoster vaccine.