Problem: Health-risk behaviors contribute to the leading causes of morbidity and mortality among youth and adults in the United States. In addition, significant health disparities exist among demographic subgroups of youth defined by sex, race/ethnicity, and grade in school and between sexual minority and nonsexual minority youth. Population-based data on the most important health-related behaviors at the national, state, and local levels can be used to help monitor the effectiveness of public health interventions designed to protect and promote the health of youth at the national, state, and local levels. Reporting Period Covered: September 2016–December 2017. Description of the System: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-related behaviors among youth and young adults: 1) behaviors that contribute to unintentional injuries and violence; 2) tobacco use; 3) alcohol and other drug use; 4) sexual behaviors related to unintended pregnancy and sexually transmitted infections (STIs), including human immunodeficiency virus (HIV) infection; 5) unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence of other health-related behaviors, obesity, and asthma. YRBSS includes a national school-based Youth Risk Behavior Survey (YRBS) conducted by CDC and state and large urban school district school-based YRBSs conducted by state and local education and health agencies. Starting with the 2015 YRBSS cycle, a question to ascertain sexual identity and a question to ascertain sex of sexual contacts were added to the national YRBS questionnaire and to the standard YRBS questionnaire used by the states and large urban school districts as a starting point for their questionnaires. This report summarizes results from the 2017 national YRBS for 121 health-related behaviors and for obesity, overweight, and asthma by demographic subgroups defined by sex, race/ethnicity, and grade in school and by sexual minority status; updates the numbers of sexual minority students nationwide; and describes overall trends in health-related behaviors during 1991–2017. This reports also summarizes results from 39 state and 21 large urban school district surveys with weighted data for the 2017 YRBSS cycle by sex and sexual minority status (where available). Results: Results from the 2017 national YRBS indicated that many high school students are engaged in health-risk behaviors associated with the leading causes of death among persons aged 10–24 years in the United States. During the 30 days before the survey, 39.2% of high school students nationwide (among the 62.8% who drove a car or other vehicle during the 30 days before the survey) had texted or e-mailed while driving, 29.8% reported current alcohol use, and 19.8% reported current marijuana use. In addition, 14.0% of students had taken prescription pain medicine without a doctor’s prescription or differently than how a doctor told them to use it one or more times during their life. During the 12 months before the survey, 19.0% had been bullied on school property and 7.4% had attempted suicide. Many high school students are engaged in sexual risk behaviors that relate to unintended pregnancies and STIs, including HIV infection. Nationwide, 39.5% of students had ever had sexual intercourse and 9.7% had had sexual intercourse with four or more persons during their life. Among currently sexually active students, 53.8% reported that either they or their partner had used a condom during their last sexual intercourse. Results from the 2017 national YRBS also indicated many high school students are engaged in behaviors associated with chronic diseases, such as cardiovascular disease, cancer, and diabetes. Nationwide, 8.8% of high school students had smoked cigarettes and 13.2% had used an electronic vapor product on at least 1 day during the 30 days before the survey. Forty-three percent played video or computer games or used a computer for 3 or more hours per day on an average school day for something that was not school work and 15.4% had not been physically active for a total of at least 60 minutes on at least 1 day during the 7 days before the survey. Further, 14.8% had obesity and 15.6% were overweight. The prevalence of most health-related behaviors varies by sex, race/ethnicity, and, particularly, sexual identity and sex of sexual contacts. Specifically, the prevalence of many health-risk behaviors is significantly higher among sexual minority students compared with nonsexual minority students. Nonetheless, analysis of long-term temporal trends indicates that the overall prevalence of most health-risk behaviors has moved in the desired direction. Interpretation: Most high school students cope with the transition from childhood through adolescence to adulthood successfully and become healthy and productive adults. However, this report documents that some subgroups of students defined by sex, race/ethnicity, grade in school, and especially sexual minority status have a higher prevalence of many health-risk behaviors that might place them at risk for unnecessary or premature mortality, morbidity, and social problems (e.g., academic failure, poverty, and crime). Public Health Action: YRBSS data are used widely to compare the prevalence of health-related behaviors among subpopulations of students; assess trends in health-related behaviors over time; monitor progress toward achieving 21 national health objectives; provide comparable state and large urban school district data; and take public health actions to decrease health-risk behaviors and improve health outcomes among youth. Using this and other reports based on scientifically sound data is important for raising awareness about the prevalence of health-related behaviors among students in grades 9–12, especially sexual minority students, among decision makers, the public, and a wide variety of agencies and organizations that work with youth. These agencies and organizations, including schools and youth-friendly health care providers, can help facilitate access to critically important education, health care, and high-impact, evidence-based interventions.