In response to cholera outbreaks in London during 1853-1854, John Snow conducted an historic investigation that launched the field of modern epidemiology [1]. Snow hypothesized that unsanitary conditions caused by sewage dumped into city cesspools contaminated local drinking water, resulting in the rapid spread of Cholera. To test his hypothesis, he collected data from Londoners who acquired and did not acquire cholera, paying close attention to where individuals who contracted cholera lived and acquired their water. Almost all individuals who acquired cholera drank from wells that were near cesspools in or near the Soho district of London. One well in particular, "the Broad Street pump," was a primary water source for hundreds of cholera victims in Soho. To intervene, Snow persuaded London city officials to remove the handle from the Broad Street pump to prevent townspeople from consuming the contaminated water. After doing so, the cholera epidemic ceased. Snow's investigation provides a good starting point for understanding the epidemiology of HIV in the southern United States ("the South"). Epidemiology is the study of the distribution and determinants of disease, and it is the "core science of public health." [2] Like Snow did with cholera in the 1850s, the HIV prevention workforce uses epidemiology to identify persons who are at greatest risk for acquiring and transmitting HIV (distribution) and the reasons why (determinants). Epidemiologic data tell us, for example, that persons most at risk for HIV infection are gay, bisexual, and other men who have sex with men (MSM); African Americans; Latinos; transgender women; and, as evidenced by the articles in this special issue, persons in the South [3]. To inform intervention approaches, our workforce uses epidemiology in attempts to prevent behaviors that most commonly result in HIV infection: condomless sex, injection drug use, and nonadherence to HIV antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) [4].