The incidence of serious neurologic complications after organ and stem cell transplantation can be as high as 20% to 30%, with most occurring in the early posttransplant period. Encephalopathy often results from metabolic disturbances and immunosuppressant drug neurotoxicity but can also occur with central pontine myelinolysis and other lesions of the central nervous system (CNS). Seizures are also common and can be related to drug toxicity or herald CNS disorders. A thorough evaluation of any patient who develops seizures or mental status changes after transplantation is warranted to distinguish transient reversible causes from serious CNS disorders.