Drug utilization review (DUR) is a tool for monitoring the appropriateness of physicians' prescribing patterns. The present systematic overview was undertaken to determine the extent of appropriate use of oral quinolones, cephalosporins, and macrolides in nonacute-care settings in North America reported in published DUR studies. Potentially relevant DURs conducted since 1987 were retrieved from an electronic search of 6 databases (augmented by manual searches of bibliographies of appropriate articles) and from personal communications with local experts. Independent reviewers applied objective criteria to select the DURs for inclusion. Quality assessments were performed by 4 independent reviewers using the Edmonton Quality Assessment Tool for Drug Utilization Reviews, an instrument developed to assess the potential for systematic bias in a DUR. Data from the studies included were abstracted independently by 2 reviewers using a standard data-collection form. Twelve of 587 (2.0%) articles met the inclusion criteria. Eight studies targeted the appropriateness of prescriptions for ciprofloxacin (appropriateness range, 5% to 95%), 3 included cephalosporins (range, 0% to 100%), and 2 examined erythromycin (40%). There were 2 primary reasons for a rating of inappropriate: (1) the prescription was not first-line therapy, or (2) there was insufficient documentation in the patient record. The designation inappropriate did not mean that the drug did not benefit the patient. Of the 4 intervention-based DURs, 1 study showed a significant improvement in appropriate use. Because of heterogeneity in study design, delivery of interventions, and outcome assessment, a pooled estimate of effect was not derived. Four studies estimated the cost of inappropriate prescribing to the institutional study site, which ranged from $20,500 to $173,359 annually; however, these estimates cannot be generalized because of various limitations. When the 12 studies were assessed for methodologic quality, 1 study was rated as high, 7 as moderate, and 4 as low. Levels of prescribing appropriateness reported in the DUR literature should be interpreted cautiously. The DUR studies included in this review varied greatly in the methodologic rigor applied to sample selection, standardized data collection, application of standardized screening criteria, and validated data analysis.