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Effective anti-crime policies hinge on correctly identifying the mechanisms that underlie the etiology of criminal behavior, which in turn requires accurate and precise characterizations of the underlying mechanism’s organized set of entities and activities (Proctor and Niemeyer, Forthcoming). As its nomenclature suggests, strain plays a fundamental role in general strain theory’s (GST) explanation of crime (Agnew 1992; 2006); nonetheless, the framework’s characterization of the concept of strain—both in of itself and in terms of the causal role it plays within the larger theory—lacks critical detail. In this paper, we illustrate how research within the field of neuroendocrinology can dramatically improve GST’s characterization of strain, as well as the role chronic strain plays in increasing the propensity of individuals to engage in criminal coping behavior. Moreover, we also show how the integration of neuroendocrinology research into general strain theory provides a critical point of integration between general strain, self-control, and social control theories. We conclude by contrasting the benefits of our biologically-informed, mechanistic approach to that of the gene-environment interaction models currently offered by biosocial criminology (e.g., Stogner 2015).