Pharyngitis is one of the most common infectious diseases affecting children. Group A streptococci are the leading bacterial cause of pharyngitis in children and adults. Because inappropriate antibiotic treatment for pharyngitis is becoming a major issue, only true group A beta-hemolytic streptococcus (GABHS) infections, proven by rapid antigen test or culture, should be treated with antibiotics. GABHS pharyngitis is often a mild and self-limiting infection in the absence of antimicrobial therapy. However, antimicrobial treatment must be administered to eradicate the pathogen from the throat, limit the spread of the infection and prevent possible progression to rheumatic fever, suppurative disease or toxin-mediated complications. Penicillin V for 10 days is the standard therapy and is effective in the management of GABHS pharyngitis. However, there are drawbacks to penicillin V therapy, including the length of the dosing regimen, which are leading to decreasing penicillin prescription rates in many countries. In addition bacteriologic treatment failures have been documented in up to 35% of GABHS patients treated with penicillin V, particularly in children <6 years old. A number of mechanisms may be responsible for these failures, but poor compliance with the standard 10-day penicillin treatment is likely to be a major factor. There is growing evidence to suggest that children with GABHS pharyngitis can be effectively treated with non-penicillin V antibiotics, which have the advantage of simpler and shorter dosing regimens compared with penicillin V. Among the antibiotics that have been tested clinically, azithromycin is the most widely studied. A total dose of 60 mg/kg azithromycin, given either as 12 mg/kg once daily for 5 days or 20 mg/kg once daily for 3 days, provides the best rate of GABHS eradication. Thus a total dose of 60 mg/kg azithromycin given during 3 or 5 days constitutes an alternative treatment to standard penicillin therapy in cases of penicillin hypersensitivity, when patient nonadherence to a 10-day penicillin regimen is suspected or for patients who fail therapy with a beta-lactam.