BACKGROUND Primary care physicians are challenged by the need to stay abreast of current research on a wide variety of topics in an environment of time constraints, evolving literature, and misinformation on health topics that are sometimes promulgated to the public. OBJECTIVE We sought to identify and discuss common clinical situations encountered in primary care for which medical reversals have occurred. METHODS We recently identified almost 400 medical practices that were used in clinical care before they were tested in well-done randomized controlled trials and subsequently were found to be ineffective or harmful. RESULTS We review several of these practices commonly used in family medicine, which include arthroscopy for osteoarthritis of the knee, opioids for common causes of pain, and aspirin and continuous positive airway pressure for the prevention of cardiovascular disease. CONCLUSIONS Although these practices were implemented because of sound biologic plausibility or encouraging observational data, well done randomized controlled trials have failed to show evidence of effectiveness. These examples raise caution in introducing new clinical interventions into widespread clinical practice without sufficient high-quality evidence demonstrating efficacy.