Since the introduction of antibiotics 6 decades ago, clinicians have taken comfort in the relative safety and exceptional efficacy of these drugs. Patients initially looked on antibiotics as “wonder drugs,” primarily because of their life-saving benefits in treating serious wounds, postsurgical infections, pneumonia, meningitis, endocarditis, and sepsis, as well as their dramatic effect on sexually transmitted infections and infections of the urinary tract. Antibiotics are available for use in the community with oral formulations, as well as in the hospital with parenteral preparations. Over the past several decades, antibiotics have been used enthusiastically by physicians, and patients have learned to expect them for the treatment of many ailments, even those that are known not to be caused by bacteria. It is widely believed that more than half of the community use of antibiotics is for the treatment of respiratory infections in children, well more than half of which are caused by viruses. Antibiotics have been used for decades in the treatment of acne vulgaris and many other common skin conditions and have been used adjunctive to surgical drainage for a large number of deeper cutaneous and fascial abscesses and carbuncles. That antibiotics are frequently prescribed in response to patient requests for these miracle drugs to treat trivial or nonbacterial infections and that most physicians are very comfortable prescribing these agents by telephone for presumed but not proven bacterial infections are understatements. Initially, sulfonamides and penicillins dominated the field, but cephalosporins and penicillinase-resistant semisynthetic penicillins soon followed. Macrolides and tetracyclines were also introduced relatively early during the history of antibiotics as broad-spectrum agents for a variety of indications. The development of macrolides included the introduction of clarithromycin and the azalide azithromycin, both of which had improved tolerability and activity. Tetracyclines were