Purpose: To learn about African American older adults' knowledge and perceptions of brain donation, factors that relate to participating or not participating in a brain donation research program, and methods to increase African American brain donation commitment rates in the context of an Alzheimer's disease (AD) research program. Design and Methods: African American older adults (n = 15) from the Boston University Alzheimer's Disease Core Center participant research registry enrolled in 1 of 2 focus groups of 90 min about brain donation. Seven participants were selected for a third follow-up focus group. Results: Focus group transcripts were analyzed using consensual qualitative research methods, and 8 overarching themes emerged: (a) perceptions of and misconceptions about brain donation procedures, (b) racial minorities in medical research, (c) racial disparities and discrimination in medical settings, (d) influence of religion and spirituality, (e) family perceptions of and involvement in donation, (f) family history of disease and desire to find a cure, (g) prior exposure to medical and research settings, and (h) culturally sensitive approaches to brain donation. Implications: Culturally relevant educational protocols need to be created for use with African American older adults. These protocols should include information about brain donation procedures, rates of AD among Black elders, and potential benefits of donation to Black communities; inclusion of religious figures, family, and peers in donation education and decisions; and methods to address mistrust, including cultural competence trainings for staff.