NSAIDs are the analgesics that are most commonly used world-wide. In the past few years, there have been significant advances in explaining the mechanism of action and clinical efficacy of the drugs belonging to this pharmacological family. Recent data relating to the role of cyclo-oxygenase (COX)-2 in the development of neuronal hyperexcitability and pain hypersensitivity have opened new perspectives in our understanding of the therapeutic effects of these drugs in several painful conditions. The main objective of this brief review is to deal with some physiopathological and pharmacological aspects concerning the role of NSAIDs, with special reference to COX-2 inhibitors, in the treatment of pain.