Cytomegalovirus (CMV) continues to cause major complications after hematopoietic cell transplantation (HCT). Over the past decade, most centers have adopted preemptive antiviral treatment or prophylaxis strategies to prevent CMV disease. Both strategies are effective but also have shortcomings with presently available drugs. Here, we review aspects of CMV treatment and prevention in HCT recipients, including currently used drugs and diagnostics, ways to optimize preemptive therapy strategies with quantitative polymerase chain reaction assays, the use of prophylaxis, management of CMV disease caused by wild-type or drug-resistant strains, and future strategies.