There is epidemiological observation that long-term treatment of patients suffering from rheumatoid arthritis with ibuprofen results in reduced risk and delayed onset of Alzheimer's disease (AD). Chronic central nervous system inflammation in AD brain is implicated in the pathology, but how ibuprofen impacts the pathogenic AD pathways is unclear. Ibuprofen, a commonly used over-the-counter nonsteroidal anti-inflammatory drug (NSAID) that is a cyclooxygenase (COX)-1 and COX-2 inhibitor as well as a peroxisome proliferator-activated receptor (PPAR) agonist, decreases the production of nitric oxide (NO), protects neurons against glutamate toxicity and decreases the production of proinflammatory cytokines. Ibuprofen crosses the blood brain barrier and suppresses neuritic plaque pathology and inflammation in AD brain. Furthermore, ibuprofen is a potent free radical scavenger, and it could reduce lipid peroxidation and free radical generation. Because of neuroprotective activity, relative safety, and its long history of use, ibuprofen is currently being developed for clinical use in AD. Ibuprofen may be a promising new therapeutic avenue for the treatment of neurodegenerative diseases such as AD.