Adoptive transfer of antiviral effector or memory CD8 T cells is a therapeutic option for preventing acute cytomegalovirus (CMV) disease after primary or recurrent infection in immunocompromised recipients of hematopoietic stem cell transplantation (HSCT) aimed at curing hematopoietic malignancies. Preclinical research in murine models has demonstrated the power of CD8 T-cell-based preemptive immunotherapy and has encouraged clinical trials that gave promising results. The clinical evidence, however, is based primarily on statistical analyses indicating a reduced incidence of CMV-associated complications. Here, we will briefly review the data obtained from the murine model showing that CD8 T cells derived from CMV-immune donors and administered either as peptide-selected cytolytic T lymphocyte lines or after ex vivo purification by T-cell-receptor-specific cell sorting can indeed prevent CMV-mediated histopathology and multiple organ failure.