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Some individuals that experience a traumatic event are vulnerable, and others resilient. We have had a long-standing interest in psychological/behavioral factors that foster resilience and the neural mechanisms that mediate the effects of these variables. We have found that the presence of behavioral control overran adverse event blunts the impact of that adverse event, and protects the organism against the negative effects of later stressors, even if they are uncontrollable. Investigation of the underlying neural mechanism(s) focuses on 2 key issues—which neural circuits detect/process the presence of control, and how is this information then used to modulate the impact of negative events to produce resiliency in the present and future. The medial prefrontal cortex is a focus in the study of both issues. The experimental strategies utilize intersectional optogenetic and chemogenetic approaches.