Acanthamoeba-related cerebral abscess and encephalitis are rare but usually fatal, being caused by free-living amoebic infections usually occurring in immunocompromised patients. In patients receiving transplants, a literature review showed that the infection is universally fatal. The diagnosis is often missed despite appropriate investigations including lumbar puncture, computerized tomography, and brain biopsy. We present the first reported liver transplant patient with Acanthamoeba cerebral abscess. The diagnosis was made in brain tissue removed at decompressive frontal lobectomy. He was successfully treated with a 3-month course of co-trimoxazole and rifampicin. There was no recurrence of the disease after 11 years of follow-up. Liver Transpl 14:308–312, 2008. © 2008 AASLD.