Development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) has been ongoing since 1994, though official release will not occur for another 4 years. Potential revisions are being derived from multiple sources, including building on perceived limitations of DSM-IV; broad-based literature reviews; secondary and primary data analyses; and discussions between global members of the mental health community. The current focus on aligning DSM with the International Classification of Diseases-11 (ICD-11) speaks to the importance of creating a unified text that embraces cross-cutting issues of diagnostics, such as developmental, age-related, and cultural phenomena. International discourse is vital to this process and has been fostered by a National Institutes of Health-sponsored conference series on diagnosis-specific topics. From this series, the DSM-V Task Force developed the following set of revision principals to guide the efforts of the DSM-V Work Groups: grounding recommendations in empirical evidence; maintaining continuity with previous editions of DSM; removing a priori limitations on the amount of changes DSM-V may incur; and maintaining DSM’s status as a living document. With work group formation complete, members are currently carrying out the research and revision recommendations proposed during the conference series. Ongoing activities include adding specialized advisors to each work group; completing literature reviews and planning data analyses; and forming study groups to discuss integration of cross-cutting issues (e.g., developmental lifespan factors; formation of diagnostic spectra). The road to DSM-V and ICD-11 has been challenging, but members continue to work diligently in their goal of constructing the most harmonious, scientifically sound, and clinically relevant DSM to date.