Aspirin and the non-steroidal anti-inflammatory drugs (NSAIDs) have been commercially available for decades, and their ability to reduce pain and inflammation is well established. It was first shown nearly 30 years ago that aspirin strongly inhibits platelet function by acetylation of platelet cyclo-oxygenase (COX) at the functionally important amino acid serine 529. This prevents access of the substrate (arachidonic aid) to the catalytic site of the enzyme at tyrosine 385 and results in irreversible inhibition of platelet dependent formation of thromboxane, a powerful promoter of aggregation, for the lifetime of the platelet (7–10 days). Aspirin is about 150–200-fold more potent as an inhibitor of the constitutive isoform of the platelet enzyme (COX-1) than the inducible isoform (COX-2), which is expressed by cytokines, inflammatory stimuli, and some growth factors.¹ This explains the different dose requirements of aspirin as an antithrombotic (COX-1) and an anti-inflammatory drug (COX-2).² Non-aspirin NSAIDs inhibit the activity of both COX-1 and COX-2 by reversibly blocking the access of arachidonic acid to the active site at the apex of a hydrophobic channel within these enzymes.¹ Acetaminophen is a weak, non-selective inhibitor of both COX enzymes, although the precise mechanism of action remains elusive. It has been recently proposed that it might act to reduce the active, oxidised form of both the COX enzymes, which would make it more potent at sites that have low peroxide concentrations, such as the brain and spinal cord.³ Aspirin and NSAIDs are non-selective inhibitors of both COX-1 and COX-2, whereas newer agents termed “coxibs” are selective inhibitors of COX-2.⁴ The identification of COX-2 selective inhibitory NSAIDs was thought to be a major breakthrough, with the expectation of a significant reduction in side effects. The major controversy with respect to the COX-2 selective inhibitors as a class has been …