Treatment guidelines from the Infectious Diseases Society of America, the American Heart Association, and the American Academy of Pediatrics recommend only oral penicillin V or intramuscular benzathine penicillin G as the treatments of choice for group A beta-hemolytic streptococcal pharyngitis. Practitioners prescribe amoxicillin most frequently for children. Ten-day treatment courses with first-generation oral cephalosporins or erythromycin are recommended as suitable alternatives in patients who are allergic to penicillin. Yet oral cephalosporins are used as drugs of choice for many patients with group A beta-hemolytic streptococcal pharyngitis. This review examines the evidence in order to help the practitioner choose the optimal antibiotic treatment for their patients.