This Viewpoint seeks to examine current psychiatric nosology through the lens of modern philosophy of science.¹ Elsewhere I have strongly defended, in both philosophical and moral terms, the reality of major mental illness as an aggregate category.² However, the status of our current nosologic categories is much less clear. Many scientific theories assume constructs that are not directly observable (muons, genetic drift) but whose existence is inferred. In mental health research, psychiatric diagnoses play such a role. We assume that constructs, such as schizophrenia or alcohol use disorder, exist but we can only observe the signs, symptoms, and course of illness that we postulate result from these disorders. Despite years of research, we cannot explain or directly observe the pathophysiologies of major mental health disorders that we could use to define essential features.