Purpose of review Patients diagnosed with cancer are at risk of viral reactivation, namely herpes simplex virus (HSV), varicella-zoster virus (VZV) and/or cytomegalovirus (CMV). However, the risk varies significantly with underlying malignancy and treatment regimen. We review the latest evidence for antiviral prophylaxis strategies, focusing on novel immune therapies and future directions. Recent findings Antiviral prophylaxis is indicated for all high-risk patients. The approval of letermovir for CMV prophylaxis has significantly reduced the burden of clinically significant infections in allogeneic hematopoietic stem cell transplant (alloHCT) recipients, and recent data now supports use up to 200 days posttransplant. For intermediate-risk regimens such as myeloma therapies and autologous hematopoietic stem cell transplant (autoHCT), antiviral prophylaxis is also a cornerstone of VZV prevention. Newer chimeric antigen receptor (CAR) T-cell and bispecific antibody (BsAb) therapies are increasingly available; while HSV/VZV prophylaxis has been incorporated into trial and real-world treatment protocols, optimal duration is unclear and data on CMV reactivation is still emerging. Solid tumours are a lower risk cohort, but high-dose steroids, immune checkpoint inhibitors and radiotherapy can increase the risk of viral reactivation and, therefore, close clinical monitoring is warranted. Summary As the cancer treatment landscape evolves, ongoing research into optimal antiviral prophylaxis approaches is necessary to improve patient outcomes.