In the United States, Black men who have sex with men (MSM) are disproportionately affected by HIV/AIDS. Thus, there is a need to understand the challenges facing health departments and community-based organizations responding to the HIV epidemic among this population. We interviewed 71 AIDS program directors, health department staff, and leaders of community-based organizations in 9 states and the District of Columbia. Participants identified psychosocial factors, a lack of capacity-building efforts, and stigma as barriers to HIV prevention responses targeting Black MSM. Participants identified culturally competent staff and culturally sensitive interventions as facilitating prevention responses. To ensure that HIV/AIDS interventions targeting Black MSM are effective, it is imperative to solicit the perceptions of frontline workers in health departments and community-based organizations.