Streptococcus pyogenes or Group A Streptococcus (GAS) is a major Gram-positive human pathogen that causes diverse human diseases with a high morbidity and mortality worldwide. The development of an effective GAS vaccine is hindered by the occurrence of many unique GAS serotypes, the complexity of the global epidemiology of GAS infections, and safety concerns over the cross-reactivity of some antigen-specific antibodies with human tissues and proteins. Although no licensed GAS vaccine is available, a number of candidate vaccines have been or are being evaluated in laboratory or in clinical trials. This minireview provides brief information on the progress and difficulty in the development of GAS vaccines.