The group A streptococcus (GAS) (Streptococcus pyogenes) is among the most common and versatile of human pathogens. It is responsible for a wide spectrum of human diseases, ranging from trivial to lethal. The advent of modern techniques of molecular biology has taught much about the organism's virulence, and the genomes of several GAS types have now been deciphered. Surface structures of GAS including a family of M proteins, the hyaluronic acid capsule, and fibronectin-binding proteins, allow the organism to adhere to, colonise, and invade human skin and mucus membranes under varying environmental conditions. M protein binds to complement control factors and other host proteins to prevent activation of the alternate complement pathway and thus evade phagocytosis and killing by polymorphonuclear leucocytes. Extracellular toxins, including superantigenic streptococcal pyrogenic exotoxins, contribute to tissue invasion and initiate the cytokine storm felt responsible for illnesses such as necrotising fasciitis and the highly lethal streptococcal toxic shock syndrome. Progress has been made in understanding the molecular epidemiology of acute rheumatic fever but less is understood about its basic pathogenesis. The improved understanding of GAS genetic regulation, structure, and function has opened exciting possibilities for developing safe and effective GAS vaccines. Studies directed towards achieving this long-sought goal are being aggressively pursued.