Unresponsive patients with or without catatonic motor signs are etiologically heterogeneous, and all require a comprehensive neurodiagnostic assessment to rule out organic causes. Most cases prove to be due to primary psychiatric disorders, mostly mood disorders, especially mania, rather than schizophrenia. These patients respond to lorazepam administered by any route and, failing this, electroconvulsive therapy. Those patients with associated fever and autonomic instability are medical emergencies and need urgent treatment.