Failure to awaken after general anesthesia is a rare complication that may be caused by residual drug effect, systemic abnormalities, or neurologic injury. Failure to awaken often is initially attributed to residual drug effect, potentially delaying correct diagnosis. Three cases of failure to awaken because of neurologic injury are reviewed. Differential diagnosis of failure to awaken is discussed, and the importance of distinguishing pathologic causes from residual anesthetic is stressed.