Aspirin was introduced into medicine over a century ago and has become the most popular drug in the world. Although the first hypersensitivity reaction was described soon after aspirin had been marketed, only recently a phenomenon of cysteinyl leukotriene overproduction brought new insights on a balance between pro- and anti-inflammatory mediators derived from arachidonic acid. We describe the most common clinical presentations of aspirin hypersensitivity, i.e. aspirin-induced asthma, rhinosinusitis and aspirin-induced urticaria. We also present their biochemical background. Despite relatively high incidence of these reactions, aspirin hypersensitivity remains underdiagnosed worldwide. Acute reactions of aspirin hypersensitivity are elicited via cyclooxygenase inhibition by non-steroid anti-inflammatory drugs. Coxibs, selective inhibitors of cyclooxygenase-2 isoenzyme, do not precipitate symptoms in susceptible patients. Though hypersensitivity correlates with cyclooxygenase-1 inhibition, diminished tissue expression was described only for cyclooxygenase-2. Aspirin-induced asthma and aspirin-induced urticaria, in a substantial part of the patients, are driven by a release of mediators from activated mast cells. These cells in physiological conditions are under inhibitory control of prostaglandin E2. The origin of aspirin hypersensitivity remains unknown, but accumulating data from genetic studies strongly suggest that environmental factor, possibly a common viral infection, can trigger the disease in susceptible subjects.