We analyze what is known and unknown about the contribution of the pharmacist as patient educator, physician consultant, and agent to affect patient outcomes in ambulatory settings. The need for pharmacist services is discussed, as are the theoretical underpinnings and quality of the scientific evidence to support their efficacy. The analysis is conducted in the context of a shift in pharmacists' roles from product to patient orientation as well as recent U.S. legislation mandating enhanced pharmacists' roles via drug utilization review for all Medicaid patients. We conclude with a research and action agenda, calling for stronger research designs in evaluating pharmacists' interventions. The shifting paradigm in the pharmacy profession, coupled with the implementation of the Omnibus Budget Reconciliation Act of 1990, provide unique opportunities for rigorous evaluations of pharmacists as agents of change for rational drug therapy.