The need to decrease excess antibiotic use in ambulatory practice has been fueled by the epidemic increase in antibiotic-resistant Streptococcus pneumoniae. The majority of antibiotics prescribed to adults in ambulatory practice in the United States are for acute sinusitis, acute pharyngitis, acute bronchitis, and nonspecific upper respiratory tract infections (including the common cold). For each of these conditions-especially colds, nonspecific upper respiratory tract infections, and acute bronchitis (for which routine antibiotic treatment is not recommended)-a large proportion of the antibiotics prescribed are unlikely to provide clinical benefit to patients. Because decreasing community use of antibiotics is an important strategy for combating the increase in community-acquired antibiotic-resistant infections, the Centers for Disease Control and Prevention convened a panel of physicians representing the disciplines of internal medicine, family medicine, emergency medicine, and infectious diseases to develop a series of "Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults." These principles provide evidence-based recommendations for evaluation and treatment of adults with acute respiratory illnesses.This paper describes the background and specific aims of and methods used to develop these principles. The goal of the principles is to provide clinicians with practical strategies for limiting antibiotic use to the patients who are most likely to benefit from it. These principles should be used in conjunction with effective patient educational campaigns and enhancements to the health care delivery system that facilitate nonantibiotic treatment of the conditions in question.