Nonsteroidal anti-inflammatory drug (NSAID)–induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAIDinduced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAIDexacerbated cutaneous disease, nonsteroidal anti-inflammatory drug–induced urticaria/angioedema (NIUA), and single NSAID–induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID– induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema.