Acanthamoeba is the most common cause of granulomatous amebic encephalitis, a typically fatal condition that is classically described as indolent and slowly progressive. We report a case of Acanthamoeba encephalitis in a kidney transplant recipient that progressed to death within 3 days of symptom onset and was diagnosed at autopsy. We also review clinical characteristics, treatments, and outcomes of all published cases of Acanthamoeba encephalitis in solid organ transplant (SOT) recipients. Ten cases were identified, and the infection was fatal in 9 of these cases. In 6 patients, Acanthamoeba presented in a fulminant manner and death occurred within 2 weeks after the onset of neurologic symptoms. These acute presentations are likely related to immunodeficiencies associated with solid organ transplantation that result in an inability to control Acanthamoeba proliferation. Skin lesions may predate neurologic involvement and provide an opportunity for early diagnosis and treatment. Acanthamoeba is an under-recognized cause of encephalitis in SOT recipients and often presents in a fulminant manner in this population. Increased awareness of this disease and its clinical manifestations is essential to attain an early diagnosis and provide the best chance of cure.