© W. Montague Cobb-NMA Health Institute 2016. Background African-American women perform low levels of physical activity and are disproportionally burdened by associated cardiometabolic disease conditions (i.e., 57 % are obese, 49 % have cardiovascular disease). The marked health disparities among African-American women indicate the need for innovative strategies to promote physical activity to help attenuate the chronic disease health disparities in this high-risk population. Culturally tailoring physical activity programs to address the sociocultural norms, values, beliefs, and behaviors of African-American women is an advantageous strategy to enhance physical activity promotion efforts. The purpose of this article is to discuss critical aspects for researchers to consider when designing physical activity programs for African-American women and to present a conceptual framework to guide intervention development. Methods Development of the framework was based on our previous physical activity research with African-American women, seminal literature on the topics of cultural adaptation and health promotion, sociological and theoretical perspectives on the role of women in African-American culture, and key determinants of physical activity engagement among African-American women. Results Three key concepts are discussed in the conceptual framework: (1) Developmental milestones and life stage transitions of African-American women; (2) Historical, social, and cultural influences associated with physical activity engagement; and (3) Intervention delivery strategies. Discussion Using the framework to guide intervention development has the potential to enhance the physical activity and health outcomes of a physical activity program for African-American women.