Cytomegalovirus (CMV) is a pathogen, commonly encountered in the recipients of solid organ transplantation and is an important cause of morbidity and mortality in these patients. CMV infection and disease have been shown to increase the cost of care in transplant recipients and several different strategies of prevention have been shown to be effective in clinical trials. A systematic review of published information on the economic impact of CMV in solid organ transplantation was performed; both clinical- and decision-analysis-based studies were reviewed. Clinical studies have shown that CMV infection and disease is associated with increased length of hospital stay and overall costs. Decision-analysis-based studies suggest that in general, antiviral chemoprophylaxis against CMV in transplant recipients is a cost-effective intervention compared with other established healthcare interventions such as strategies for colorectal cancer screening. Prophylaxis with oral or parenteral ganciclovir is probably the most cost-effective strategy; however, restricting prophylaxis to high-risk groups (such as donor seropositive/recipient seronegative status and the use of an antilymphocyte antibody) or chemoprophylaxis for an extended period does not improve cost effectiveness. Pre-emptive therapy is an evolving strategy for prevention of CMV disease in transplant recipients and is rapidly gaining in popularity. Well-designed trials incorporating prospective cost data and comparing pre-emptive therapy versus conventional antiviral prophylaxis are needed to establish the superiority of one strategy over the other.