The brain is the central organ for adapting to experiences whether or not we call them “stressful”. With adaptation, the brain changes its architecture and alters systemic function via regulation of neuroendocrine, autonomic, immune, and metabolic systems. Those systems, in turn, alter brain structure and function, including their effects upon higher cognitive function, mood, and self-regulation. The healthy brain has a considerable capacity for resilience in the aftermath of stressors or health damaging behaviors but when it “gets stuck” it may need external intervention. This is based upon its ability to respond to interventions designed to open “windows of plasticity” and redirect its function toward better health,. There are no magic bullets and drugs cannot substitute for targeted interventions that help an individual become resilient, of which mindfulness-based stress reduction and meditation are emerging as useful tools. Because of the multimorbidity of disorders involving both brain and body, it is urgent to incorporate into “precision medicine” a better understanding of how epigenetically-induced individual differences and current experiences affect the efficacy of pharmacological, behavioral and psychosocial interventions.