Abstract: The multidrug-resistant organism and Clostridium difficile epidemics, which are adverse consequences of antibiotic use, continue to grow. Antibiotic stewardship—a program aimed at the judicious use of antibiotics—is a deterrent. Yet, its implementation, whether through prospective audit with intervention and feedback or by formulary restriction and preauthorization, experiences the underuse of clinical guidelines for when antibiotics should be withheld and withdrawn. This article is the first to catalog and summarize the guidelines for controlling antibiotic overuse to facilitate their implementation. Conditions for which antibiotics are not justified include nonbacterial respiratory syndromes, asymptomatic bacteriuria, colonization and culture contamination, selected cases of acute otitis media and skin and soft tissue infections, and “low-grade” fever. Traditionally accepted durations should be shortened for acute exacerbations of chronic bronchitis, pneumonias, urinary tract infections, intra-abdominal infections, Staphylococcus aureus bacteremia, and surgical prophylaxis. Studies demonstrate that guideline implementation through antibiotic stewardship can enhance outcomes and decrease resistance. Unfamiliarity with the guidelines should be addressed by their more widespread dissemination. Their imperfections should be addressed by more placebo-controlled trials. Concerns of undertreatment need to be counterbalanced by the adverse consequences of overtreatment. We believe that regulatory agencies should consider promoting antibiotic stewardship.