OBJECTIVE: This review examines the issues surrounding short-course antimicrobial therapy of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis, acute (suppurative) otitis media, and acute sinusitis. BACKGROUND: Accumulating evidence suggests that short-course (ie, < or = 5 days) antimicrobial therapy may have equivalent or superior efficacy compared with traditional longer (10- to 14-day) therapies. RESULTS: In GABHS tonsillopharyngitis, short-course therapy with 6 days of amoxicillin, 4 or 5 days of various cephalosporins, and 5 days of azithromycin (10 mg/kg once daily on all 5 days in pediatric patients) are all reasonable alternatives to traditional 10-day penicillin therapy. In uncomplicated acute (suppurative) otitis media, single-dose intramuscular ceftriaxone or 3- to 5-day short-course oral antimicrobial therapy should be effective in > or = 80% of patients. However, more research is needed in children aged <2 years, since short-course therapy may not be successful in most patients in this population. In sinusitis, most short-course therapy data have involved acute maxillary disease in adult patients. Preliminary results are encouraging, but more study is needed, especially in children. CONCLUSIONS: Cost-containment in antimicrobial therapy should include consideration of short-course therapy in the management of upper respiratory tract infections.