The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) developed by the American Psychiatric Association (1994) is a compelling effort at a best approximation to date of a scientifically based nomenclature, but even its authors have acknowledged that its diagnoses and criterion sets are highly debatable. Well-meaning clinicians, theorists, and researchers could find some basis for fault in virtually every sentence, due in part to the absence of adequate research to guide its construction. Some points of disagreement, however, are more fundamental than others. The authors discuss issues that cut across individual diagnostic categories and that should receive particular attention in DSM-V: (a) the process by which the diagnostic manual is developed, (b) the differentiation from normal psychological functioning, (c) the differentiation among diagnostic categories, (d) cross-sectional vs. longitudinal diagnoses, and (e) the role of laboratory instruments.