Cytomegalovirus (CMV) is the most common opportunistic viral infection to occur following solid-organ transplantation. This review will discuss the current strategies of management of CMV in solid-organ transplantation and their challenges. There are two principal approaches for preventing CMV disease in recipients of solid-organ transplants: prophylactic and pre-emptive. Ganciclovir is the most studied and used antiviral for both treatment and prevention, and is the first-line treatment for CMV infection and CMV disease in transplant recipients. There is no consensus regarding the most appropriate prevention method and the approach to CMV disease prevention differs among transplantation centers owing to the paucity of data comparing the two strategies head-to-head. Currently, the recommended treatment for CMV disease is intravenous ganciclovir.