Four types of therapeutic strategies for managing cytomegalovirus (CMV) in solid organ transplant recipients, the mechanisms of action and efficacy of drugs used for prophylaxis, and the criteria for evaluating drugs for inclusion in a formulary are described. Universal and selective prophylaxis are simple to implement and effective for CMV prophylaxis, but they are costly and patient nonadherence and viral resistance can develop. Preemptive therapy may cause less resistance and cost less, but it is more complex and associated with a higher incidence of infection, which may have no effect on secondary effects from CMV infection, and higher recurrence of disease than prophylactic therapy. Treatment of active disease may be less costly for the drug than other approaches, but intravenous access is required and the rates of infection recurrence and mortality are higher compared with prophylaxis and preemptive therapy. Criteria for deciding which CMV prophylactic drugs to include in a formulary include efficacy, safety, convenience, and cost. CMV immune globulin i.v. is costly and exhibits reduced efficacy when used alone in patients at high risk for CMV disease. Intravenous ganciclovir is effective, but it is costly because of infusion costs. Intravenous drug therapies are inconvenient and associated with a risk of bacterial and fungal infection. Oral acyclovir is safe to use and inexpensive (since a genetic exists), but it has poor efficacy and is inconvenient because of the need for four large daily doses. Valacyclovir is more convenient and with similar safety and probably better efficacy than acyclovir, but it is more costly. Oral ganciclovir and oral valganciclovir have similar safety and costs, with greater efficacy than acyclovir. The single daily dose and lack of resistance to valganciclovir are advantages over oral ganciclovir, which requires three daily doses and can result in the development of resistance.