Accumulating evidence suggests that aging is associated with dysregulated immune and inflammatory responses. Investigation into the cellular and molecular mechanisms underlying this phenomenon suggests that an up-regulated cyclooxygenase (COX)-2 expression, and resulting increase in production of prostaglandin E2 (PGE2), is a critical factor. Macrophages from old mice have significantly higher levels of PGE2 production compared with those from young mice, a result of increased COX-2 expression and protein levels leading to increased COX enzyme activity. Further, it is possible that the age-associated increase in macrophage PGE2 production is due to ceramide-induced up-regulation of nuclear factor-kappa B activation. Such processes may also occur in cell types other than macrophages, lending further insight into potential mechanisms of age-related disease. More research is necessary to determine the efficacy of nutrient/dietary modifications, such as antioxidants and lipids, for reducing the age-related increase in COX activity and PGE2 production that are associated with several disease states.