The mainstay of medical therapy for acute and subacute sinusitis is the selection of an antimicrobial agent based on an appreciation of the usual bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Amoxicillin is appropriate therapy for patients with uncomplicated sinusitis in geographic areas in which the prevalence of beta-lactamase-producing pathogens is less than 20%. If a patient does not respond to amoxicillin or in areas in which there is a high prevalence of beta-lactamase-producing bacterial species, alternative antimicrobials include amoxicillin-clavulanate, erythromycin-sulfisoxazole, trimethoprim-sulfamethoxazole, cefaclor, cefuroxime axetil, and cefixime. Cefixime, which is less active against S. pneumoniae than most of these antimicrobials, should be reserved for patients who do not improve with amoxicillin. Amoxicillin-potassium clavulanate, cefuroxime axetil, and erythromycin-sulfisoxazole have the most comprehensive antibacterial spectra.