Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used drugs but their use is hampered by gastrointestinal side effects. Cyclo-oxygenase Inhibitor Nitric Oxide Donors (CINODs) are a new class of anti-inflammatory and analgesic drugs generated by adding a nitric oxide generating moiety to the parent NSAID via an ester linkage. The combination of balanced inhibition of the two main COX isoforms with release of NO confers to CINODs a reduced gastrointestinal toxicity and a potent anti-inflammatory activity. It is suggested that the NO, which is released by the metabolism of nitrate as the compounds are broken down, may counteract the consequences of the NSAID-induced decrease in gastric mucosal prostaglandins. Recent clinical trials with CINODs (previously termed NO-NSAIDs) have provided data consistent with pre-clinical observations.