Described here is a patient with medically intractable generalized epilepsy who developed status epilepticus (SE) affecting his right cerebral hemisphere for about 48 hours, which led to irreversible injury to that hemisphere. His partial SE did not respond to the first-line therapies, repeated doses of midazolam, or continuous intravenous infusion of propofol. Extensive investigations failed to find a cause of his SE except for a low serum valproic acid. A minor trauma that he suffered 1 week prior to his SE was of questionable significance. Neurological examination, neuropsychological testing, electroencephalography, and magnetic resonance imaging all demonstrated striking abnormalities limited to the affected cerebral hemisphere that did not resolve with repeated testing. This case illustrates permanent focal brain injury following prolonged partial SE in a patient with previously known generalized seizure disorder.