Previous studies of the immune control of cytomegalovirus infection have primarily focused on analysis of the traditional adaptive T-cell response. Donadeu et al. bring a new perspective through evaluation of multiple adaptive and innate immune subtypes in parallel with cytomegalovirus-specific cell-mediated immunity in a prospective cohort of kidney transplant recipients with findings validated in 2 independent studies. Identification of a natural killer T-cell subtype associated with cell-mediated immunity and freedom from cytomegalovirus infection demonstrates the importance of the coordinated innate and adaptive immune response for effective viral control.