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The introduction and combination of more-potent immunosuppressive regimens, and the increased transplantation of organs into more severely ill patients, have again placed cytomegalovirus (CMV) disease in the spotlight of posttransplantation complications. Both direct and associated complications related to CMV need to be considered in understanding the pathogenesis of CMV infection after solid-organ transplantation. New diagnostic methods with higher sensitivity for the detection of CMV and the ability to quantify CMV indicate that low levels of CMV replication are present in many patients who don't have clinical symptoms ascribed to CMV infection. How these low levels of CMV replication impact the outcome of the transplanted graft remains unknown. In addition, there needs to be further study regarding whether only patients at high risk for developing CMV disease or, also, those with clinically asymptomatic levels of CMV replication should be the target of effective preventive regimens. This review summarizes our current knowledge of the pathogenesis of CMV infection after solid-organ transplantation, and it outlines different effective preventive regimens and approaches.