© 2014 Wiley Periodicals, Inc. Human herpesvirus-6 (HHV-6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV-6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV-6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV-6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV-6 encephalitis may be important for affected patients. We report the case of a 53-year-old pancreas-after-kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV-6B encephalitis in solid organ transplant recipients.