Antibiotic resistance has rapidly become one of the most significant challenges facing modern health care. Despite widespread public education efforts by the national government and health organizations worldwide, there remains a significant lack of public understanding of antibiotic resistance, how to prevent it and the implications if the science and health care communities fail to find a solution. The Centers for Disease Control and Prevention (CDC) and the American College of Physicians (ACP) recently published updated guidelines for appropriate antibiotic use in upper respiratory tract infections. These guidelines include several key recommendations for acute bronchitis, pharyngitis and acute rhinosinusitis (including the common cold). In the United States, at least 2 million antibiotic-resistant illnesses and 23,000 deaths occur each year. These illnesses and deaths result in a large cost to patients, payers and health care institutions. Recent research has shown that numerous human factors, such as patient satisfaction and pressure on prescribers, have an impact on inappropriate antibiotic prescribing. The Infectious Diseases Society of America (IDSA) has published information on the key elements of a model antimicrobial stewardship program. Pharmacists can use this information to help reduce inappropriate use of antibiotics and reduce the spread of antimicrobial resistance.