Cytomegalovirus (CMV) viremia from reactivation of latent infection is a common complication after allogeneic hematopoietic cell transplantation (HCT). Untreated, CMV viremia can progress to affect other organs, resulting in organ dysfunction with high morbidity and mortality. In this issue of theJCI, Prockop and authors demonstrate that third-party donor T cells sensitized ex vivo to CMV pp65-derived overlapping pentadecapeptides are safe and effective for the treatment of CMV reactivation or CMV disease refractory to first-line pharmacotherapies occurring after HCT. They also provide insight into the biological differences between responders and nonresponders. This work confirms the utility of third-party CMV pp65 VSTs and suggests strategies for further improving the efficacy of this cell-therapy approach.