Research advances in psychiatric genetics have raised expectations that genetic findings might lead to major breakthroughs in psychiatric nosology. The author reviews the plausibility of these claims. Four areas are addressed. First, it is argued that familial aggregation of a single putative psychiatric syndrome provides at best limited evidence for the validity of that syndrome. Second, both traditional and molecular genetic strategies can supply important insights into major diagnostic conundrums. However, evidence that one or a few individual genes impact on risk for two disorders is not likely to resolve definitively the nosologic relationship between the two syndromes. Third, while gene-based essentialist models for psychiatric disorders are conceptually appealing, they are not well supported empirically. Gene discovery in psychiatry is, on its own, unlikely to allow us to "carve nature at its joints," thereby validating categorical psychiatric diagnoses. Fourth, the project to ground "messy" psychiatric categories on the firm foundation of genes--as an archetypal natural kind--may be fundamentally flawed because the very concept of "the gene" as a discrete entity is itself increasingly in doubt. Whereas psychiatric genetics has and will continue to provide important insights into the etiology of psychiatric and substance use disorders, it is not likely alone to provide deep answers to the complex and multifaceted problems facing psychiatric nosology. 10.1176/appi.ajp.163.7.1138
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