Ganciclovir is a nucleoside analogue which is used to treat and prevent cytomegalovirus (CMV) infection. Most recent clinical studies of ganciclovir in transplant recipients have focused on preventive approaches. When ganciclovir was last reviewed in Drugs in 1994, substantial data on post-transplantation CMV prophylaxis with this drug were available only for patients undergoing allogeneic bone marrow transplantation (BMT). Two strategies had emerged: prophylaxis for all patients or early treatment started after detection of asymptomatic CMV infection. Subsequently, a large double-blind study has shown that ganciclovir prophylaxis is more effective than early treatment in preventing early CMV disease after allogeneic BMT and is not associated with an increased incidence of neutropenia. However, mortality for the 2 strategies was similar. The efficacy of prophylactic intravenous ganciclovir in liver transplant recipients [including high risk donor seropositive/recipient seronegative (D+/R-) or antilymphocyte-treated patients] is now well established. Prophylaxis with oral ganciclovir was effective both overall and in D+/R-patients in a large placebo controlled study, and prolonged intravenous ganciclovir was significantly more effective than high dose aciclovir (acyclovir) in seropositive liver recipients. Early treatment with ganciclovir has proved useful in this setting. More limited data indicate that CMV prophylaxis with intravenous ganciclovir may be useful after heart or lung transplantation but its value in D+/-patients remains unclear. Combined chemoimmunotherapy may be valuable in these high risk patients but controlled data are lacking. Targeted prophylaxis with intravenous ganciclovir is effective in renal transplant recipients receiving antilymphocyte therapy; the role of oral ganciclovir in this setting is less clear. The value of ganciclovir in D+/- renal transplant recipients and its efficacy compared with high dose aciclovir have not been determined. Ganciclovir is the only antiviral chemotherapy which reduces the risk of CMV infection or disease after most types of major transplantation. Unresolved issues include the best (and most cost-effective) use of ganciclovir and aciclovir after allogeneic BMT, the efficacy of oral ganciclovir compared with other anti-CMV regiments, the potential clinical effect of viral resistance during prolonged ganciclovir exposure and the value of ganciclovir in certain high risk transplant populations. In the meantime, ganciclovir has an important role in the prevention of CMV infection and disease after bone marrow and liver transplantation and is likely to gain wider clinical use in heart, lung and kidney transplant recipients.