A major goal for the next edition of the APA Diagnostic and Statistical Manual for Mental Disorders (DSM-V) is to take advantage of the multidisciplinary research advances in mental health that have occurred worldwide since the publication of DSM-IV and ICD-10. Toward this end, APA has devoted an extended period of time for research planning in advance of DSM-V. This process involved an assessment of the current state-of-the-science in relevant fields, an assessment of knowledge gaps, and the production of short- and long-term research agendas to stimulate new research. To accomplish these goals, we initiated a “White Paper” process focusing on cross-cutting issues, followed by a National Institutes of Health (NIH)-sponsored conference series coordinated with the American Psychiatric Institute for Research and Education (APIRE) and the World Health Organization (WHO)—to assess the emerging research basis for revising specific diagnostic categories. We have now initiated the DSM-V Task Force and Diagnostic Workgroups, which will build on these past developments in an ongoing collaborative effort with the international research community and the WHO-guided ICD-11 advisory process. The developmental process for this edition of DSM will be discussed as will the potential changes in a conceptual framework for the classification of mental disorders.