The etiology of acute otitis media and sinusitis has evolved over the past decade. Streptococcus pneumoniae is the causative pathogen less often now than in the past in many parts of the United States, and two gram-negative bacteria, Haemophilus influenzae and Moraxella catarrhalis, are increasingly important. Both of these organisms often produce beta-lactamase and, therefore, may resist eradication by amoxicillin. Increasingly, the clinical situation emerges whereby an alternative antimicrobial is sought to improve therapeutic efficacy. The choices include trimethoprim-sulfamethoxazole, cefaclor, cefuroxime axetil, amoxicillin-clavulanate, cefixime, cefprozil, loracarbef, cefpodoxime proxetil, clarithromycin, and azithromycin. Selecting among these alternatives requires a knowledge of their antimicrobial spectrum, side effect profile, dosing frequency, and cost. The etiology of pharyngitis has also become a topic of renewed research. Penicillin treatment failure occurs in 10-30% of group A beta-hemolytic streptococcal (GABHS) throat infections. A possible role for other pharyngeal microflora to protect GABHS from eradication through elaboration of beta-lactamase in the tonsillopharyngeal milieux is an intriguing hypothesis. As a consequence, alternative antibiotics that are able to resist beta-lactamase action are receiving attention as rational therapeutic choices in GABHS treatment.