This paper presents a biopsychosocial model of self-regulation, executive functions, and personal growth that we have applied to Goal-Directed Resilience in Training (GRIT) interventions for posttraumatic stress disorder (PTSD), obesity, and chronic pain. Implications of the training for the prevention of maladaptation, including psychological distress and health declines, and for promoting healthy development are addressed. Existing models of attention, cognition, and physiology were sourced in combination with qualitative study findings in developing this resilience skills intervention. We used qualitative methods to uncover life skills that are most salient in cases of extreme adversity, finding that goal-directed actions that reflected an individual’s values and common humanity with others created a context-independent domain that could compensate for the effects of adversity. The efficacy of the resilience skills intervention for promoting positive emotion, enhancing neurocognitive capacities, and reducing symptoms was investigated in a randomized controlled trial with a veteran population diagnosed with PTSD. The intervention had low attrition (8%) and demonstrated improvement on symptom and wellbeing outcomes, indicating that the intervention may be efficacious for PTSD and that it taps into those mechanisms which the intervention was designed to address. Feasibility studies for groups with comorbid diagnoses, such as chronic pain and PTSD, also showed positive results, leading to the application of the GRIT intervention to other evocative contexts such as obesity and chronic pain.