Individual differences in the aging process can be conceptualized as an accumulation of wear and tear of daily experiences and major life stressors that interact with the genetic constitution and predisposing early life experiences. The neuroendocrine system, autonomic nervous system, and immune system are mediators of adaptation to challenges of daily life, referred to as allostasis, meaning "maintaining stability through change." Physiological mediators such as adrenalin from the adrenal medulla, glucocorticoids from the adrenal cortex, and cytokines from cells of the immune system act upon receptors in various tissues and organs to produce effects that are adaptive in the short run but can be damaging if the mediators are not shut off when no longer needed. When release of the mediators is not efficiently terminated, their effects on target cells are prolonged, leading to other consequences that may include receptor desensitization and tissue damage. This process has been named "allostatic load," and it refers to the price the tissue or organ pays for an overactive or inefficiently managed allostatic response. Therefore, allostatic load refers to the "cost" of adaptation. This article discusses the mediators of allostasis and their contributions to allostatic load as well as their role in resilience of the aging organism to stressful experiences.