Rates of invasive group A streptococcal (GAS) infections in the United States (U.S.) have increased from approximately 10,000-13,000 cases each year to nearly 19,000 and 1700 deaths in 2016. Concurrent and likely contributing to this upsurge has been an increase in previously uncommon strains such as emm types 26, 49, and 89—strains which may have been amplified through outbreaks among the homeless and illicit drug users in multiple urban areas. The proportion of persons with invasive GAS reported to the Centers for Disease Control and Prevention’s (CDC) laboratory- and population-based surveillance who are identified as using intravenous drug use has doubled from an average of 5% of cases over the last 10 years to 11% in 2016, concurrent with a national epidemic of opioid use. The U.S. has also seen an increase in reported small clusters and extensive outbreaks in long-term care facilities (LTCFs). Outbreaks among this vulnerable population and among illicit drug users are often initially unrecognized and difficult to control. CDC has begun using whole genome sequencing (WGS) as a tool to supplement outbreak investigations and our public health response to invasive GAS infections. We have developed an outbreak detection tool for use in our national invasive GAS surveillance covering a population of approximately 34 million persons; refinement and validation of the tool is ongoing. WGS has been used to help elucidate potential transmission chains in persistent LTCF outbreaks and may be useful in outbreaks among marginalized populations