This article provides information on the pathogenesis of aspirin hypersensitivity, cross-sensitivity, and cross-tolerance of different NSAIDs in patients with respiratory types of reactions. Hypersensitivity to aspirin may affect 5-20% of patients with chronic asthma and an unknown fraction of patients with chronic urticaria-angioedema. These patients develop cross-reactions to other, chemically non-related, NSAIDs with strong inhibitory activity towards cyclo-oxygenase (COX)-1 (e.g. indomethacin, naproxen, ketoprofen). Avoidance of aspirin and all cross-reacting NSAIDs as well as education of patients are crucial. As an alternative antipyretic or analgesic drug, aspirin-sensitive asthmatic patients may take acetaminophen (paracetamol) in low or moderate doses (<1000mg). Preferential COX-2 inhibitors (nimesulide, meloxicam) are tolerated by the majority but not all hypersensitive patients. Selective COX-2 inhibitors (celecoxib and rofecoxib [withdrawn from the market]) are well tolerated by almost all aspirin-sensitive asthmatic patients. In patients with coronary artery disease requiring treatment with aspirin, desensitization to aspirin may be an alternative approach. Thus, for the majority of patients with asthma and hypersensitivity to aspirin or other NSAIDs, an alternative anti-inflammatory drug can be found. However, in each individual case physicians must consider the choice of an alternative NSAID carefully.