Fat embolism syndrome (FES) is a well-known sequela of long-bone fracture and fixation. FES most commonly affects the pulmonary system. Brain emboli may lead to a symptomatic cerebral fat embolism (CFE), which is devastating. In this article, we review the presentation, causes, and management of FES presenting with CFE, report a case, and review the literature. The case involved an otherwise healthy 42-year-old woman who developed CFE after reamed intramedullary nail fixation of femoral and tibial shaft fractures during a single operation. When the patient presented after surgery, she was nonverbal and was having diffuse extremity weakness. The diagnosis was stroke and resultant diffuse encephalopathy secondary to CFE. Within days of urgent management, the patient's cognitive and ophthalmologic deficits were substantially improved. Six months after surgery, cognitive and ophthalmologic recovery was excellent, and the fractures were healing with good functional recovery in the affected limb.