1. Monika L. Dietrich, MD* 2. Russell W. Steele, MD†,‡ 1. *Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 2. †Department of Pediatrics, Ochsner Health Center for Children, New Orleans, LA 3. ‡University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA * Abbreviations: ANF: : acute necrotizing fasciitis ARF: : acute rheumatic fever GAS: : group A Streptococcus IVIG: : intravenous immunoglobulin MRSA: : methicillin-resistant Staphylococcus aureus MSSA: : methicillin-susceptible S aureus PANDAS: : pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections PSGN: : poststreptococcal glomerulonephritis STSS: : streptococcal toxic shock syndrome 1. Clinical prediction rules for group A Streptococcus pharyngitis are unreliable in children, and unless viral etiology is strongly suspected, throat swab with a rapid antigen detection test should be performed. 2. Avoid “proof of cure” cultures when treating pharyngitis. 3. Clindamycin is important in invasive group A Streptococcus infection for toxin mediation but should not be used alone secondary to possible resistance. After completing this article, readers should be able to: 1. Understand the epidemiology, transmission, and major virulence factors of group A Streptococcus (GAS) infections. 2. Plan the appropriate diagnostic evaluation of suspected GAS infection. 3. Recognize the clinical features of, and major complications associated with, invasive and noninvasive GAS infections. 4. Plan appropriate management for a patient with a GAS infection. In 1933, Rebecca Lancefield changed our understanding of β-hemolytic streptococci by developing a system of serologic classification based on the carbohydrate composition of cell wall antigens. Of these organisms, the most significant in human pathogenicity is group A Streptococcus (GAS), otherwise known as Streptococcus pyogenes . (1) GAS is responsible for an impressively wide variety of clinical manifestations, from noninvasive infections, such as pharyngitis, scarlet fever, erysipelas, and cellulitis, to invasive disease, including sepsis, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis (Table 1). It has also been linked to multiple nonsuppurative complications including acute rheumatic fever (ARF), poststreptococcal glomerulonephritis (PSGN), and the controversial pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Globally, an estimated 18 million people are suffering from a serious GAS-related illness, with about 1.78 million new cases annually. Hundreds of millions of people develop less serious GAS infection every year, placing a massive burden on healthcare systems. The …