The human cytomegalovirus is widely prevalent among human population and it is the most common viral pathogen that affects both the graft's and solid-organ transplant recipient's survival. The risk is highest in donor-seropositive, recipient-seronegative pairing transplantation. These recipients carry increased risk of developing symptomatic primary CMV infection; however, other risk factors may have an impact on cytomegalovirus activation as well: intensity of immunosuppression, type of organ transplanted, rejection and/or treatment for rejection, HLA-mismatch between recipient and donor, certain HLA-types of the recipient, female sex etc. Cytomegalovirus infection in transplant patients has been associated with both direct (symptoms) and indirect effects which are derived from the immunomodulating impact of the virus such as cellular effects and cytokine expression or systemic immune suppression leading to other opportunistic infections. Prevention of the direct and indirect effects of cytomegalovirus infection is the therapeutic goal in transplanted patients. Most transplant centers use either universal prophylaxis or preemptive therapy to prevent the infection. The advantages and disadvantages of these two preventive strategies and current evidence-based recommendations for preventing cytomegalovirus disease in solid-organ transplant recipients are discussed according to others' and the authors' own observations. According to recommendations of the American and Canadian Societies of Transplantation, most of the centers--after analyzing of the CMV-infection risk factors of the recipients--divide them into three groups: high-, moderate- and low-risk groups. The preventive strategy is attached to the risk-group type. In the high-risk group (R-/D+ and lung transplant patients) the use of the universal prophylaxis is necessary. The patients administered anti-lymphocyte antibodies (ATG, ALG or OKT3) need selective (subtype of universal) prophylaxis. Among the moderate-risk patients (R+/D+ or R+/D-) the doctors may choose either universal prophylaxis or preemptive therapy. Selection of a strategy requires consideration of patient-specific factors as well as practical considerations such as available resources. For avoidance of the indirect effects of CMV infection universal prophylaxis is preferred. The use of preventive proceedings in low-risk patients is the matter of the center's decision.