The development of clinical practice guidelines has spread from utilization review agencies to physician specialty societies, federal agencies, managed care organizations, and academic health centers as their usefulness in accomplishing the goals of healthcare reform become clear. The author reviews the mounting evidence that variation in the practice of medicine suggests that patients in some areas are not receiving all needed services, while others are receiving unnecessary services. He explores the implications of practice guidelines for improving the quality of care while controlling cost. Practice guidelines are defined and distinguished from medical review criteria. The author explores the challenges in governance, funding, and guideline development and communication that will have to be overcome to establish the credibility of practice guidelines. Finally, he addresses the opportunities for the osteopathic medical profession to establish its uniqueness in this setting.