Purpose of Review <p>This paper proposes a stress-response framework for understanding substance use in the context of adversity, integrating fight (resistance), flight (adaptive coping), freeze (maladaptive coping), and fawn (strategic assimilation/appeasement) responses, with resilience as a moderating factor.</p> Recent Findings <p>Evidence indicates that adaptive resistance and coping can protect against substance use, while maladaptive resistance, maladaptive coping, and fawning may increase long-term risk despite short-term relief. Resilience, both individual and collective, can buffer adversity’s effects and enhance positive stress responses, though measurement and conceptual inconsistencies limit cross-study synthesis.</p> Summary <p>Advancing research on adversity and substance use requires the use of validated measures, the simultaneous assessment of multiple stress responses to capture their interactions, and greater theorization of resistance and fawning/strategic assimilation, which remain underdeveloped and understudied in substance use research.</p>