Varicella zoster (VZV) and herpes simplex (HSV) viruses commonly cause self-limited infection of the skin and mucous membranes. However, certain groups of subjects, including neonates, cancer patients, organ and bone marrow transplant recipients and those with congenital or acquired deficiencies of cell mediated immunity, are at increased risk for dissemination of either virus to the lungs and/or other viscera. The highest risk for VZV pneumonitis is in bone marrow transplant recipients, 44%, and in children with acute leukemia, 32%. The mortality from this complication of VZV infection in the preantiviral era was at least 25%. Except for neonates, dissemination and mortality rates for HSV infections are less than for VZV infections in the high risk groups. Cell-mediated immunity has a major role in both recovery from primary infection and modulation of latent infection, but antiherpes antibodies also have an important role in moderating the extent and severity of infection. Both viruses cause a patchy nodular pneumonia with scattered necrotic and hemorrhagic foci. Physical examination is often misleading and rapid progression of pneumonia can occur within hours. Intravenous acyclovir, administered early in the course of HSV and VZV infection at dosages of 250 mg/m2 and 500 mg/m2 every eight hours, respectively, has nearly eliminated the risk of severe symptomatic pneumonitis. Treatment of established pneumonitis with acyclovir at these doses has also reduced the mortality of herpesvirus pneumonias.