This research synthesis examined HIV/AIDS surveillance and health care financing data and reviewed relevant research literature to describe HIV epidemiology, outcomes, funding, and contributing factors to the HIV epidemic in the Southern USA with particular focus on a group of Southern states with similar demographic and disease characteristics and comparable HIV epidemics (Alabama, Georgia, Florida, Los Angeles, Mississippi, North Carolina, South Carolina, Tennessee, and Texas). These states are hereafter referred to as "targeted Southern states." Eight of the 10 states with the highest HIV diagnosis rates in 2011 were in the Southern USA; six were targeted states. Forty-nine percent of HIV diagnoses were in the South in 2011, which contains only 37% of the US population. The targeted states region had the highest HIV diagnosis rate than any other US region in 2011. The South was also found to have the highest HIV-related mortality and morbidity rates in the USA. The high levels of poverty, HIV-related stigma, and STDs found in the South, particularly in the targeted Southern states, likely contribute to greater HIV incidence and mortality. The disproportionate impact of HIV in the South, particularly among targeted states, demonstrates a critical need to improve HIV prevention and care and address factors that contribute to HIV disease in this region.