Although antimicrobial agents from a number of classes have been used with a good degree of clinical success for acute bacterial exacerbations of chronic bronchitis, the incidence of resistance by beta-lactamase-producing strains to certain penicillins and cephalosporins continues to increase and represents a growing clinical problem. There also have been reports of significant resistance by Streptococcus pneumoniae to tetracyclines and of treatment failures caused by this organism among patients receiving fluoroquinolones. The emergence of penicillin-resistant pneumococci in North America also is of concern. Although first-generation cephalosporins are no longer regarded as first-line therapy or optimal alternatives for acute exacerbations of chronic bronchitis, more recently developed agents of this class have better activity against the primary pathogens, and their efficacy and safety have been demonstrated in a number of clinical trials. Newer macrolide agents probably should be reserved for infections caused by atypical organisms.