Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and syphilis, are increasing in the United States. This roundtable will provide an overview of the new 2021 CDC STI Treatment Guidelines, with special focus on syphilis and issues related to the correctional setting. These guidelines have evolved from a quick treatment guide into a comprehensive clinical management resource. Given the challenging nature of syphilis diagnosis and management, several syphilis case scenarios will be reviewed and discussed.