The history of the DSM process demonstrates the triumph of the biomedical model with DSM-III in 1980. That landmark document introduced a symptom-based, descriptive approach to diagnosis, with operational definitions of the diagnostic categories accomplished through the use of diagnostic criteria. The manual mostly achieved the desired goal of reliability in diagnostic across treatment and research settings. It was assumed that diagnostic validity, using the Robins/Guze criteria published 10 years before DSM-III, would follow for the DSM-III categories in the years following publication in 1980. The story of the ensuing decades is that of validity failure, with the unavoidable conclusion that the diagnostic categories do not represent real phenotypes. This chapter details the history of the failure to achieve Robins/Guze validity, the failed efforts of the DSM-5 Task Force and Work Groups to fill in the breach with a variety of measures, and, using analytic, philosophy of science tools—natural-kind analysis and complexity theory—what psychiatric nosology might look like in the future.