Stress is a state of the mind, involving both brain and body as well as their interactions; it differs among individuals and reflects not only major life events but also the conflicts and pressures of daily life that alter physiological systems to produce a chronic stress burden that, in turn, is a factor in the expression of disease. This burden reflects the impact of not only life experiences but also genetic variations and individual health behaviors such as diet, physical activity, sleep, and substance abuse; it also reflects stable epigenetic modifications in development that set lifelong patterns of physiological reactivity and behavior through biological embedding of early environments interacting with cumulative change from experiences over the lifespan. Hormones associated with the chronic stress burden protect the body in the short run and promote adaptation (allostasis), but in the long run, the burden of chronic stress causes changes in the brain and body that can lead to disease (allostatic load and overload). Brain circuits are plastic and remodeled by stress to change the balance between anxiety, mood control, memory, and decision making. Such changes may have adaptive value in particular contexts, but their persistence and lack of reversibility can be maladaptive. However, the capacity of brain plasticity to effects of stressful experiences in adult life has only begun to be explored along with the efficacy of top-down strategies for helping the brain change itself, sometimes aided by pharmaceutical agents and other treatments.