The Centers for Disease Control and Prevention (CDC) has released Sexually Transmitted Infections Treatment Guidelines, 2021. This document provides current evidence-based diagnostic, management, and treatment recommendations, and serves as a source of clinical guidance for managing sexually transmitted infections (STIs). It includes notable updates from the 2015 guidance including treatment on chlamydia, trichomoniasis, pelvic inflammatory disease, uncomplicated gonorrhea in neonates, children, and other specific clinical situations. It also builds on broader treatment changes that were published in Morbidity and Mortality Weekly Report late last year.