This article provides a narrative review of studies that examined mechanisms of behavior change in substance use disorder. Several mechanisms have some support, including self-efficacy, craving, protective behavioral strategies, and increasing substance-free rewards, whereas others have minimal support (e.g., motivation, identity). The review provides recommendations for expanding the research agenda for studying mechanisms of change, including designs to manipulate putative change mechanisms, measurement approaches that expand the temporal units of analysis during change efforts, more studies of change outside of treatment, and analytic approaches that move beyond mediation tests. The dominant causal inference approach that focuses on treatment and individuals as change agents could be expanded to include a molar behavioral approach that focuses on patterns of behavior in temporally extended environmental contexts. Molar behavioral approaches may advance understanding of how recovery from substance use disorder is influenced by broader contextual features, community-level variables, and social determinants of health.