For African Americans in the southern United States, the social determinants of health are influenced by a unique history that encompasses hundreds of years of slavery, injustices during the Jim Crow era, the Great Migration, the civil rights era, and contemporary experiences like the Black Lives Matter movement. Black activists, physicians, and communities continue to battle inequities and structural problems that include poverty, inadequate access to health care, incarceration, a lack of transportation, and food insecurity. As the result of redlining and other historical and contemporary injustices, African Americans are less likely to own a home or to have equity, which places them in danger of financial ruin if they experience an illness such as a heart attack, stroke, or cancer, for which they are often at greater risk due to many social and environmental factors. At the same time, African American communities display many strengths and are often very resilient against these structural inequities. With essays spanning topics from culturally appropriate health care to faith-based interventions and the role of research networks in addressing disparities, this collection is pivotal for understanding the health of African Americans in the South.