There is an urgent need to transform basic research discoveries into tools for treatment and prevention of mental illnesses. This article presents an overview of the National Institute of Mental Health (NIMH) programs and resources to address the challenges and opportunities in psychiatric drug development starting at the point of discovery through the early phases of translational research. We summarize NIMH and selected National Institutes of Health (NIH) efforts to stimulate translation of basic and clinical neuroscience findings into novel targets, models, compounds, and strategies for the development of innovative therapeutics for psychiatric disorders. Examples of collaborations and partnerships among NIMH/NIH, academia, and industry are highlighted.