Infections due to group A streptococci (GAS) represent a public health problem of major proportions in both developing and developed countries. Currently available methods of prevention are either inadequate or ineffective, as attested to by the morbidity and mortality associated with this ubiquitous pathogen worldwide. Advances in molecular biology have shed new light on the pathogenesis of GAS infections and have identified a number of virulence factors as potential vaccine targets. Therefore, the National Institute of Allergy and Infectious Diseases convened an expert workshop in March 2004 to review the available data and to explore the microbiologic, immunologic, epidemiologic, and economic issues involved in development and implementation of a safe and effective GAS vaccine. Participants included scientists and clinicians involved in GAS research, as well as representatives of United States federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, Department of Defense, and National Institute of Allergy and Infectious Diseases), the World Health Organization, and the pharmaceutical industry. This report summarizes the deliberations of the workshop.