For years, intravenous ganciclovir has been the recommended treatment for cytomegalovirus (CMV) in transplant recipients. Recently, oral valganciclovir has been shown to induce a response to CMV similar to that produced by intravenous ganciclovir and could consequently be an alternative to ganciclovir in patients with non-severe disease. Sequential therapy with ganciclovir followed by valganciclovir, after the onset of clinical improvement, reduces costs and avoids prolonged hospital stays, thus benefitting patients. Optimal treatment duration is guided by clinical response and virological monitoring (polymerase chain reaction or antigenemia) and is maintained until the results are negative. Some groups use secondary prophylaxis in patients with risk factors for recurrence of CMV disease. Reducing the intensity of immunosuppression or complementing antiviral therapy with immunoglobulins can be considered in patients with severe disease or immunodepression. There are no conclusive data on the most effective treatment in ganciclovir-resistant CMV. Therapeutic decisions should be based on genotypic resistance studies, the patient's immune status and disease severity. Treatment consists of foscarnet alone or in combination with ganciclovir in the most severe forms and in high-resistance mutations, or in increasing the dose of ganciclovir in clinical forms or in mild resistance. There are no conclusive data on alternative antiviral drugs or complementary therapy with mTOR inhibitors. Several CMV vaccines are under development and the preclinical results are encouraging.