The 2021 CDC Sexually Transmitted Infections (STI) Treatment Guidelines update the 2015 guidelines, incorporating new recommendations for treating Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. The guidelines also include metronidazole for pelvic inflammatory disease, alternative treatments for bacterial vaginosis, management of Mycoplasma genitalium, and updated human papillomavirus (HPV) vaccine recommendations. They emphasize expanded risk factors for syphilis testing in pregnant women, one-time testing for hepatitis C, evaluation of men who have sex with men after sexual assault, and two-step testing for genital herpes. The guidelines aim to assist healthcare providers in preventing and treating STIs, emphasizing both treatment and prevention strategies. They are applicable in various healthcare settings and should be used as clinical guidance rather than prescriptive standards. The guidelines were developed through collaboration with subject matter experts and systematic literature reviews, with recommendations based on evidence from peer-reviewed studies. They include detailed clinical prevention guidance, risk assessment, counseling, and treatment strategies for STIs and HIV. The guidelines also address the importance of accurate risk assessment, prevention counseling, and the use of condoms, vaccines, and other preventive measures. They emphasize the importance of consistent and correct condom use, the role of pre-exposure prophylaxis (PrEP) for HIV, and the use of male circumcision as a risk reduction strategy. The guidelines also provide recommendations for partner services, STI screening, and the importance of follow-up care for individuals with STIs. Overall, the guidelines aim to improve the prevention and treatment of STIs and HIV through evidence-based practices and clinical recommendations.The 2021 CDC Sexually Transmitted Infections (STI) Treatment Guidelines update the 2015 guidelines, incorporating new recommendations for treating Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. The guidelines also include metronidazole for pelvic inflammatory disease, alternative treatments for bacterial vaginosis, management of Mycoplasma genitalium, and updated human papillomavirus (HPV) vaccine recommendations. They emphasize expanded risk factors for syphilis testing in pregnant women, one-time testing for hepatitis C, evaluation of men who have sex with men after sexual assault, and two-step testing for genital herpes. The guidelines aim to assist healthcare providers in preventing and treating STIs, emphasizing both treatment and prevention strategies. They are applicable in various healthcare settings and should be used as clinical guidance rather than prescriptive standards. The guidelines were developed through collaboration with subject matter experts and systematic literature reviews, with recommendations based on evidence from peer-reviewed studies. They include detailed clinical prevention guidance, risk assessment, counseling, and treatment strategies for STIs and HIV. The guidelines also address the importance of accurate risk assessment, prevention counseling, and the use of condoms, vaccines, and other preventive measures. They emphasize the importance of consistent and correct condom use, the role of pre-exposure prophylaxis (PrEP) for HIV, and the use of male circumcision as a risk reduction strategy. The guidelines also provide recommendations for partner services, STI screening, and the importance of follow-up care for individuals with STIs. Overall, the guidelines aim to improve the prevention and treatment of STIs and HIV through evidence-based practices and clinical recommendations.