Chronic stress can affect human health through a myriad of behavioral and biochemical pathways. Tauhis review focuses on some key hormonal and metabolic pathways that appear important today. In modern society, we are faced with excessive psychological stress, as well as an epidemic of overeating, and the two together appear to have synergistic effects. Chronic stress can lead to overeating, co-elevation of cortisol and insulin, and suppression of certain anabolic hormones. This state of metabolic stress in turn promotes abdominal adiposity. Both the direct stress response and the accumulation of visceral fat can promote a milieu of systemic inflammation and oxidative stress. This biochemical environment appears to be conducive to several cell aging mechanisms, mainly dampening telomerase and leading to telomere length (TL) shortening and cell senescence. Immune cell telomere shortness is linked with many chronic disease states and earlier mortality. In this way, chronic stress may influence a variety of diseases through a biochemical cascade leading to immune cell senescence. Certain psychological temperaments at high risk of this stress cascade (mainly anxiety prone), gene-environment interactions, and potential interventions for interrupting the stress-aging cascade are discussed.