Many scientific and methodological advances made in the last two decades could play an important role in the development of the dsm-5. A research agenda was coordinated with the apa, nih, and who, which led to 13 international research conferences held between 2003 - 2008. The goals of this effort have included: 1) ensuring greater clinical utility and relevance, 2) utilizing a developmental approach across the life span, 3) incorporating new knowledge from the neurosciences and the behavioral sciences in elucidating risk factors and prodromal features of disorders; and 4) adopting methodological strategies utilizing both dimensional and categorical approaches. As the Task Force for dsm and specific disorders workgroups began their activities, specific crosscutting issues are being addressed. These issues include the following topics: 1) life span developmental approaches: 2) diagnostic spectra; 3) psychiatric/ general medical interface; and 4) gender and cross-cultural expression. These activities include many international members of the workgroups. We are keenly aware of the rapidly changing research base for the description and treatment of mental disorders that include the neurodevelopmental, neurocognitive, and addictive disorders. We are re-evaluating the structure of the manual itself to facilitate both clinical practice and better research criteria to guide clinical trials, genetics, imaging, and treatment guideline developments. More specifically, we anticipate that we will have a structure that contains “receptors” for new biological, neurocognitive, and environmental risk factors as they emerge to guide future research and clinical practice. As a result, we anticipate that the dsm-5 will be a living document with a permanent revision infrastructure to enable revisions of specific diagnostic areas where new evidence is replicated and reviewed as ready for adoption. It is also vital that the dsm-5 harmonize with the icd efforts, and these joint international efforts are likely to include field trials.