The purpose of this clinical report is to provide pediatricians updated research on evidence-based sexual and reproductive health education conducted since the original clinical report on the subject was published by the American Academy of Pediatrics in 2001. Sexuality education is defined as teaching about human sexuality, including intimate relationships, human sexual anatomy, sexual reproduction, sexually transmitted infections, sexual activity, sexual orientation, gender identity, abstinence, contraception, and reproductive rights and responsibilities. Developmentally appropriate and evidence-based education about human sexuality and sexual reproduction over time provided by pediatricians, schools, other professionals, and parents is important to help children and adolescents make informed, positive, and safe choices about healthy relationships, responsible sexual activity, and their reproductive health. Sexuality education has been shown to help to prevent and reduce the risks of adolescent pregnancy, HIV, and sexually transmitted infections for children and adolescents with and without chronic health conditions and disabilities in the United States.