Adolescents and young adults continue to have the highest rates of sexually transmitted diseases. New chlamydia and gonorrhea diagnostic tests are being used in innovative ways to increase the number of infections that are detected. Nevertheless, challenges such as gonorrhea resistance and partner notification and treatment continue to hinder efforts to reduce the prevalence of these two bacterial infections. Although recent surveillance data suggest a decreasing trend of herpes simplex virus 2 (HSV-2) incidence among adolescents and young adults, the incidence of sexually transmitted human papillomavirus (HPV) in adolescent and young adult females remains high. Progress has been made toward the development of vaccines that may become available in the future to prevent infection with and sequelae from HSV-2 and HPV.