Nimesulide is a NSAID with good anti-inflammatory, analgesic and antipyretic activities expected of such compounds. However, in addition it has some unique therapeutic and pharmacological activities. The novel therapeutic aspects include a relatively low toxicity to the gastrointestinal tract and kidneys, it can be given to most patients who experience respiratory problems with other NSAIDs, and the onset of analgesia is comparatively quick. The main novel pharmacological actions obtained using nimesulide in vivo at therapeutic doses, or in vitro at concentrations within the therapeutic range of free (unbound) drug, include: a preferential inhibition of prostaglandin synthesis via COX-2, and reductions in cytokine action/release, histamine release, the release of enzymes that degrade cartilage, and the release of superoxide anions and other toxic substances from neutrophils. Interactions with other drugs are few and of little or no clinical significance.