acknowledged that despite providing significant financial resources to the scientific community, research has had limited impact on improving mental health diagnosis, prognosis, or treatment. 1 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 2 and the philosophical tradition of pragmatism, 3-5 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 6 (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.We need a road map for EPP to overcome misalignment of incentives between the 5 P's: patients, providers (individuals who provide mental health care), payers, policy makers, and problem solvers (researchers). For researchers, incentives prioritize which problems to focus on, what studies to carry out, and what to communicate among peers. Extramural funding, which is essential for academic survival and social reinforcement (ie, advancements in peer organization as a mark of academic excellence), shapes these incentives. Patients want to have symptomatic relief, to understand the nature of their condition, 7 and to be actively involved in planning and managing their chronic mental health issues. Providers need efficient ways to diagnose and treat patients, optimize available interventions for a particular patient, and keep patients satisfied. 8 Payers' incentives 9 are focused on maximizing efficiency in delivering care, minimizing cost, optimizing operations, and improving population-level mental health. Policy makers need to connect people to services, promote coordination and integration in the health care system, improve care for populations with complex needs, orient the health system toward results, and increase health system efficiencies. 10 The overlap between these incentives and priorities is small or nonexistent. For example, identifying neuroscience-based biomarkers for the severity of a mental health condition is an important goal that can be both explanatory and pragmatic. However, cost, utility, accessibility, practicality, and broad sample applicability will determine whether emerging biomarkers have any value for real clinical practice. Thus, re-