Despite lower or comparable rates of drug use than other groups, culturally significant patterns and modalities of substance use pose serious health issues for Black sexual minority men (SMM), particularly when intersecting with social adversity, high background HIV/STI prevalence, and chronic disease risk. Black SMM often experience several significant developmental precursors to substance use, including childhood trauma, minority stress, stigma, and economic hardship, all of which exacerbate drug use trajectories. A Life Course perspective helps illuminate how social determinants influence drug use behaviors over time and highlights effective approaches that mitigate harm and enhance the quality of life for Black SMM. This chapter also examines the diverse modalities through which drugs are used in the community, shedding light on how cultural norms, social networks, and situational contexts shape drug usage, meanings, and associated risks. Although primarily focused on those within the U.S. context where the most contextual and empirical data are available, this chapter also discusses how Black SMM face similar psychosocial and structural issues that affect drug use patterns globally. Where applicable, this chapter integrates insights from international studies to emphasize shared and divergent experiences among Black SMM and to draw connections across global contexts. This chapter suggests that addressing illicit drug use in this population requires moving toward social and developmental interventions that acknowledge the role of trauma and inequality, ultimately pushing the field toward effective public/global health strategies.