The hematopoietic stem cell transplantation (HSCT) setting is a rapidly evolving field, and procedures with a high degree of complexity are now entering into the clinic. The risk of developing opportunistic viral infections increases with the level of human leukocyte antigen disparity between the donor and the recipient of allogeneic HSCT and is enhanced by graft manipulations such as T-cell depletion or immune suppression required to control graft versus host disease (GVHD) or rejection. Among the opportunistic viral infections potentially hampering the outcome of HSCT, human cytomegalovirus (HCMV) infection plays a major role. In the early 1980s, before the introduction of effective antiviral treatment, HCMV disease accounted for the high mortality in recipients of allogeneic HSCT. In more recent years, the availability of HCMV-specific antiviral agents (ganciclovir, GCV, foscarnet, PFA and cidofovir, CDV) led to a dramatic decrease in HCMV-related morbidity and mortality. However, HCMV infection still remains a major concern in the HSCT setting. Historically, treatment of HCMV infection in HSCT recipients (HSCTR) evolved from treatment of overt HCMV disease to universal prophylaxis or pre-emptive treatment of active infection, in parallel with the improvement of techniques for diagnosing and monitoring HCMV infection in transplant recipients.