A paucity of relevant scientific evidence limits the ability of the primary care disciplines to practice evidence-based medicine and to advocate for health care policy. Significant barriers to primary care research still exist, including difficulties in translating practice-based wisdom into methodologically sound research, the lack of a critical mass of researchers, a poorly developed research culture, and competing demands faced by investigators. In addition, the categorical nature of most available research funding is unfavorable for the generalist focus of primary care research. Efforts to advance primary care research will require support from health care organizations, dedicated federal and state funding sources, and foundations. In addition, there is a need to provide sophisticated methodological training for a small cadre of primary care researchers while increasing opportunities for a large number of clinicians to participate in research. Opportunities for transdisciplinary collaboration need to be increased, including the creation of primary care research centers. The development of a scientific basis for primary care practice will require policy advocacy, development of infrastructure, and creative and sustained individual effort.