HIV has evolved over the past 30 years from a virtual death sentence to a chronic and manageable disease. Nurses in the United States have helped to change the epidemic through advocacy, education, care, and support for people living with HIV infection. They have contributed to the expansion of HIV prevention methods, provided support to this population and their families, and helped make HIV treatments more effective and efficient. People with HIV infection who access and remain in care can now enjoy both an improved quality of life and a greater life expectancy. Here, the authors discuss HIV epidemiology and policy in the United States, the concept of the HIV care cascade, advances in HIV testing and treatment, and how nurses can continue to have a positive impact on the HIV epidemic by encouraging testing, connecting newly diagnosed patients to specialty care, retaining these patients in long-term care, and providing access to combination antiretroviral therapy.