Epidemiologic and laboratory studies suggest that non-steroidal anti-inflammatory drug (NSAID) use reduces the risk of Alzheimer's disease (AD). Initial reports in the early 1990's indicated that a history of arthritis, a presumed surrogate of NSAID use, was associated with a lower risk of AD. [1] These reports were followed by epidemiologic studies in which NSAID use was assessed directly and the majority of these reports confirmed the inverse association with risk for AD. [2, 3] Postmortem studies in humans [4], studies in animal models of AD [5, 6], and in vitro studies [7, 8] generally support the notion that NSAIDs can reduce the deleterious inflammation which surrounds amyloid beta (Abeta) plaques in the AD brain. In addition, some studies conducted in vitro and in rodents point to a subgroup of NSAIDs that may work by inhibiting amyloidogenic APP metabolism rather than through traditional anti-inflammatory mechanisms. [9-11] This novel property of NSAIDs is currently being explored in epidemiologic studies. Results from randomized clinical trials of NSAIDs and established AD and one trial on secondary prevention have not been promising and there have been no prevention trials completed. The feasibility of using NSAIDs as a chemopreventive agent in AD is discussed.