Psychiatric medicine is now advancing from solely descriptive disease classification toward a biologically based taxonomy. This evolution is more protracted than for other branches of medicine given the complexity of the neural systems that underlie human mental function and the challenge of characterizing psychiatric phenotypes objectively and quantitatively. The ultimate goal of this exercise is to describe the mechanistic and phenotypic variability within and across traditional diagnostic boundaries in a manner that identifies risk and resilience factors, provides early detection, predicts clinical outcomes, and specifies targets for trajectory-altering therapeutics and prevention.