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Cytomegalovirus (CMV) infection is a common opportunistic infection after allogeneic haematopoietic stem cell transplantation (HSCT). CMV surveillance-preemptive therapy is the current preferred approach for preventing CMV disease after HSCT. In contrast, antiviral prophylaxis is not commonly used due to myelosuppressive effects of valganciclovir. In this article, the role of the newly approved antiviral compound, letermovir, is reviewed.Letermovir inhibits CMV by interfering viral terminase complex. In a phase 3 randomized placebo-controlled clinical study that enrolled 495 CMV-seropositive HSCT recipients, the primary end point of clinically significant CMV infection was significantly reduced by letermovir prophylaxis. Letermovir was well tolerated without risk of myelotoxicity and nephrotoxicity. Experimental in-vitro data suggest that letermovir may possess low genetic barrier to resistance. In prophylaxis trials, two breakthrough infections were reported due to selection of CMV UL56 V236M mutation.Letermovir is an important addition to the current strategies for CMV prevention after allogeneic HSCT. Its favourable efficacy and safety profile re-opens door for antiviral prophylaxis another first-line option, similar to CMV surveillance-preemptive therapy, for preventing CMV in allogeneic HSCT recipients.