Policy makers, researchers, clinicians, and the public are frustrated that research in the health sciences has not resulted in a greater improvement in patient outcomes. Our experience as clinicians and researchers suggests that this frustration could be reduced if health sciences research were directed by 5 broad principles: (1) the needs of patients and populations determine the research agenda; (2) the research agenda addresses contextual and implementation issues, including the development of delivery and accountability systems; (3) the research agenda determines the research methods rather than methods determines the research agenda; (4) researchers and clinicians collaborate to define the research agenda, allocate resources, and implement findings; and (5) the level of funding for implementation research is commensurate with and proportional to the magnitude of the task. To keep the research agenda focused on the task of improving health and to acknowledge that the effort must be seen as more comprehensive than translating or transferring research into practice (TRIP), we suggest that the task be reframed, using the term optimizing practice through research.