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Viruses are the leading cause of infections after solid organ transplant. The antiviral properties of mammalian target of rapamycin inhibitors (mTORis) have been ascribed to a variety of mechanisms and historical data have supported their use over other immunosuppressants for a myriad of viruses. Herein, we summarize the most current data to highlight the role of mTORis in the management of viral infections after solid organ transplant. The mTORis play a clear role in the management of cytomegalovirus, and have data supporting their potential use for BK virus and human herpesvirus 8–related Kaposi sarcoma. No data definitively supports mTORis for use in Epstein-Barr virus–mediated posttransplant lymphoproliferative disorder or hepatitis C virus viral replication. Although theoretically an advantageous therapy for hepatitis C virus–related liver allograft fibrosis and human immunodeficiency virus, mTORi use specifically for these indications is less attractive with modern treatments currently available. Data surrounding mTORi efficacy in preventing rejection, and their toxicity profile must be balanced with their potential antiviral effects in combination with patient-specific factors.