Age-related changes in immune function leave older adults at risk for a host of inflammatory diseases. Immune-mediated inflammatory processes are regulated by neuroendocrine hormones, including glucocorticoids, dehydroepiandrosterone, and the catecholamines, epinephrine, and norepinephrine. This regulation, however, becomes impaired in older adults in light of age-related changes in endocrine function. Chronic stress shows similarly harmful effects on neuroendocrine and immune function and may, therefore, combine with age to further increase disease risk in older adults. This article highlights evidence for the impact of age and stress on neuroendocrine regulation of inflammatory processes that may substantially increase risk for inflammatory disease at older ages.