This chapter focuses on HIV, which has been our most politically charged illness and a defining health challenge of our time. The world of HIV care over the last two decades has seen a great, almost miraculous, revolution. Today, a 35-year-old who was HIV-infected in 2018 and takes her daily medication adherently has the life expectancy of a 35-year-old without HIV infection. Monthly injections of long-acting HIV drugs look to be as good as daily pills at suppressing the virus, creating easier treatment. Despite these stunning advances, disparities in detection and care characterize the disease. The epidemic has shifted to groups that are hard to test, hard to get started on preventive care, and hard to keep on daily medication—persons who inject stimulants, men on the down-low, the mentally ill, the homeless, and the rural poor with no health insurance. Lack of information, lack of trust of providers, unfamiliarity with services, and refusals of testing and treatment due to social rejection and privacy concerns make the delivery of care more challenging for these groups. Even among persons enrolled in AIDS clinical trials who have found their way to cutting-edge medical treatment, blacks and Hispanics have poorer outcomes. As such, reaching an end to HIV will require new attention to health systems and social stigma, to geography, to housing and outreach, to the long work of public health.