The emergence of severe group A streptococcal (GAS) infection since the 1980s has now been reported from most parts of the world. Many of these cases have been associated with deep-seated infection associated with shock and multiple-organ failure and are defined as streptococcal toxic shock syndrome (StrepTSS). Strains of GAS isolated from patients with invasive disease have been predominantly of M types 1 and 3, which produce either pyrogenic exotoxin A or B or both. In this article, the clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis are presented and compared with those of StrepTSS. Current concepts about the pathogenesis of invasive streptococcal infection are also discussed, in terms of the interaction between GAS virulence factors and host-defense mechanisms. Finally, the efficacy of clindamycin, the failure of penicillin, and new ideas for future treatment of serious streptococcal infections are outlined.