In 2017, former National Institute of Mental Health Director Thomas Insel, MD, acknowledged that despite providing significant financial resources to the scientific community, research has had limited impact on improving mental health diagnosis, prognosis, or treatment. We begin a series of Viewpoints aimed at creating a road map for generating more impactful research in the future. Evidence-based pragmatic psychiatry (EPP) is an umbrella term for the application of scientific findings of and insights into mental health to improve diagnosis, prognosis, and treatment of mental health conditions. Evidence-based pragmatic psychiatry combines evidence-based medicine and the philosophical tradition of pragmatism, which evaluates the truth and utility of a proposition by the practical consequences of accepting it. However, EPP goes beyond first-generation evidence-based medicine (ie, away from rigid flowchart-based treatment approaches toward focusing on individualized evidence- and community-based care) to provide an empirically based precision medicine decision support system.