Acute pharyngotonsillitis is one of the most common infections encountered by pediatricians and family physicians. According to the US Vital Health Statistics report, acute pharyngotonsillitis is responsible for more than 6 million office visits each year by children younger than 15 years of age and an additional 1.8 million visits by adolescents and young adults aged 15 to 24 years. Most children with acute pharyngotonsillitis have symptoms that can be attributed to infection with a respiratory virus, such as adenovirus, influenza virus, parainfluenza virus, rhinovirus, and respiratory syncytial virus. However, in approximately 30% to 40% of cases, acute pharyngotonsillitis is of bacterial etiology. Group A beta-hemolytic streptococci (GABHS) are responsible for most bacterial cases of acute pharyngotonsillitis, although other pathogens, such as Neisseria gonorrhoeae, Arcanobacterium haemolyticum, Mycoplasma pneumoniae, and Chlamydia pneumoniae, may be the causative agents in sporadic cases. Pharyngotonsillitis caused by these latter pathogens can sometimes be distinguished from that caused by GABHS by considering the patient's medical history in concert with the clinical presentation. In some cases, acute pharyngotonsillitis may have an idiopathic etiology. An accurate diagnosis of GABHS infection is important because it is the only common form of acute pharyngotonsillitis for which antibiotic therapy is definitely indicated. Antibiotic therapy can shorten the clinical course of GABHS pharyngotonsillitis, reduce the rate of transmission, and prevent suppurative and nonsuppurative complications, such as peritonsillar abscess and acute rheumatic fever. Although the threat of rheumatic fever is much lower for children in the United States than in developing nations, preventing rheumatic fever and the spread of disease is the primary goal of antibiotic therapy in GABHS pharyngotonsillitis treatment and a cornerstone of practice guidelines.