Cytomegalovirus (CMV) is capable of establishing persistent or latent infection after primary infections and reactivation in immunocompromised hosts. The understanding of the nature of this latency is incomplete. The acquisition of CMV-specific immune responses appears essential for limiting primary infection and maintenance of a clinical state of latency. Host immunity induced by CMV infection includes both cellular and humoral responses. Cell-mediated responses by both CD4+ (T helper) and CD8+ cytotoxic T lymphocytes (CTLs) are detected in CMV-seropositive individuals. Studies in animal models and in immunocompromised patients have implicated deficiencies in class I MHC-restricted, CD8+CMV-specific CTL responses in the progression of experimental and human CMV infection and pneumonia. Adoptive transfer of CD8+CMV-specific CTLs in immunodeficient marrow transplant recipients provides evidence that adoptive immunotherapy with T-cell clones of defined specificity and function can be used to safely and successfully restore immunity to a human pathogen.