In solid organ transplant recipients, Epstein-Barr virus (EBV) can cause active central nervous system (CNS) infection or malignant transformation of latently infected cells in the CNS, known as post-transplant lymphoproliferative disease (PTLD). Reduction of T-cell immunosuppression is the cornerstone of management. The role of antivirals with in-vitro activity against herpesviruses in EBV-related CNS syndromes is controversial, as they have no effect on latent virus. We report an unusual case of relapsing EBV encephalitis in a donor-positive, EBV-negative renal transplant recipient, with response to valganciclovir. Our report supports the utility of antiviral treatment for EBV encephalitis, as adjunct to reducing immunosuppression, and highlights the need for a systematic approach and long-term, multi-disciplinary follow-up of such patients.