Addressing and preventing the spread of substance use disorders (SUDs) and the human immunodeficiency virus (HIV) are both vital areas of public health. Many risk factors are shared across SUD and HIV, though each present unique challenges. This product summarizes the scope of HIV in the United States and SAMHAS Region 3. It also discusses how having HIV can increase risk of substance use and how engaging in substance use can increase risk of HIV. It also shares examples of evidence-based prevention programs.