Less than 200 years ago schizophrenia emerged from a tangle of mental disorders known simply as madness. In the upcoming fifth edition of psychiatry's primary guidebook, the Diagnostic and Statistical Manual of Mental Disorders, or DSM-5, schizophrenia will finally shed the outdated, 19th-century descriptions that have characterized it to this day. Yet the disorder remains poorly understood. “There is substantial dissatisfaction with schizophrenia treated as a disease entity; its symptoms are like a fever—something is wrong, but we don't know what,” says William Carpenter, a psychiatrist at the University of Maryland and chair of the manual's Psychotic Disorders Work Group. Psychiatrists may discover that this disorder is not a single syndrome after all but a bundle of related conditions.