To review the major mechanisms of antibiotic resistance and provide an overview of currently available oral antibiotics. This article discusses the impact of antibiotic resistance on respiratory infections (eg, otitis media, sinusitis, and pneumonia) encountered in the outpatient setting and appropriate management strategies for these infections are proposed. A Medline search was performed to identify recent references from the English language pertinent to this topic. Proposed management schemes for infections due to antibiotic-resistant bacteria were derived from current literature as well as the opinion of the authors. Currently available oral antibiotics including penicillins, cephalosporins, macrolides, trimethroprim/sulfamethoxazole, and clindamycin continue to provide effective therapeutic options despite the increasing importance of antibiotic resistance in bacteria causing respiratory tract infections in the outpatient setting. The effectiveness of a given agent may no longer be assured, leading to the need for development of updated management strategies for patients experiencing treatment failure with antibiotics. Diagnostic strategies (ie, tympanocentesis) and novel treatment algorithms (eg, use of amoxicillin in combination with amoxicillin/clavulanate) for patients experiencing clinical failures potentially due to antibiotic-resistant bacteria are proposed. The increasing prevalence of antibiotic resistant bacteria (especially penicillin-resistant Streptococcus pneumoniae) is leading to new approaches to the management of common respiratory infections in the outpatient setting. Additional experience and careful clinical trials are necessary to identify optimal management strategies for these infections.