Non-steroidal anti-inflammatory drugs are the second after antibiotics group of drugs being the cause of drug hypersensitivity. The most common symptoms of nonsteroidal anti-inflammatory drugs (NSAIDs) hypersensitivity include cutaneous reactions with urticaria and angioedema and respiratory reactions (NSAIDs Exacerbated Respiratory Disease). Because in most of the cases the NSAIDs hypersensitivity is caused by non-immunological reaction due to cyclooxygenase-1 inhibition, the detailed history confirmed by challenge testing play crucial role in the diagnostics. In most of the cases reactions are evoked by the drugs having potency to inhibit cyclooxygenase-1 while drugs inhibiting specifically cyclooxygenase-2 are generally well tolerated.