Hypersensitivity to aspirin and other non steroidal anti-inflammatory drugs (NSAIDs) manifesting in the airways (rhinosinusitis, polyps, asthma) or in the skin (urticaria, angioedema) is the second most frequent untoward allergic reaction to drugs. Various aspects of this syndrome, such as its clinical features, the cell types and mediators involved, the role of underlying chronic inflammatory processes, the patterns of cross-reactivity between NSAIDs, the major role of sulfidoleukotrienes (LTC4) and of some other mediators such as prostaglandin E2 (PGE2) and C5a are briefly reviewed. It has been assumed for a long time that there were no reliable in vitro tests for that condition and that diagnostic confirmation can only be ascertained by provocation challenge. This appears no longer to be true, since several recent studies using a leukotriene release test (CAST) or a basophil activation test (BAT) on blood basophils, or a combination of both tests, yields positive results (70 - 75%) in a sizeable number of clinically validated cases, with a high specificity (above 85%). The finding in that syndrome of hyperreactive basophils suggests that the NSAID hypersensitivity syndrome is due to the associated effect of several factors : 1) Localized inflammatory processes causing a non specific cellular hyperreactivity; 2) An abnormal pharmacogenetic reaction to NSAIDs resulting in a hyperproduction of LTC4 and other mediators by activated mast cells, basophils and eosinophils.