Human herpesvirus 6 (HHV-6) infections, most commonly occurring during childhood, are frequently mild and self-limited. However, immunosuppression due to transplantation may cause reactivation of HHV-6 with manifestations ranging from fever and skin exanthem to pneumonitis, hepatitis, encephalitis, and myelitis. Because these infections may be devastating for liver transplant recipients leading to transplant organ fibrosis and failure, it is imperative that internists recognize the manifestations, establish early diagnosis, institute appropriate therapy, and make timely referrals to transplant specialists. We present a case of a 19-year-old liver transplant recipient with HHV-6 viremia, encephalopathy, and hepatitis. The patient's symptoms improved with ganciclovir and intravenous immunoglobulin treatment, serum HHV-6 copies gradually decreased, and she was discharged with outpatient follow-up. After approximately one month of antiviral therapy, the patient's viral load was undetectable. Early recognition of HHV-6 viremia, appropriate laboratory assessment, and early institution of therapy is important for internal medicine physicians to decrease morbidity and mortality in liver transplant recipients.