Recent significant contributions have been made to the understanding of Group A Streptococcus (GAS) pathogenesis. New regulatory pathways have been discovered, insight into the molecular basis of epidemics of serotype M1 disease has been obtained, the crystal structures of four toxins have been reported and a genome sequence of one GAS strain has been determined. Genome-scale approaches to the study of GAS pathogenesis are now rapidly emerging and will advance our fundamental understanding of the molecular basis of host-pathogen interactions.