This guide is based on training given by youth in Mexico, Canada, Romania, and India as a part of the RISE UP program, and provides young people with much needed free access to training resources about HIV/AIDS, substance use, and sexual health. More specifically, the guide includes basic information about HIV/AIDS and drug use; strategies for reducing sexual and drug-related harms; and issues related to the stigma and discrimination that often accompany particular sexual behaviors and drug use. The project was funded by MTV Staying Alive Foundation.