Aspirin-exacerbated respiratory disease (AERD), also known as Samter’s triad, aspirin-sensitive rhinosinusitis asthma, aspirin triad, aspirin idiosyncrasy, and nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease, is an inflammatory syndrome characterized by the combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory reactions following exposure to cyclooxygenase (COX)-1 inhibitors. Table 23.1 lists the medications that are known to inhibit COX-1 and COX-2 enzymes. In AERD patients, challenges with highly selective COX-2 inhibitors have demonstrated that these medications are well tolerated [1]. There is variable cross-reactivity among the weakly selective COX-1 inhibitors, and these reactions tend to be less severe. Settipane demonstrated 34% cross-reactivity in AERD patients with acetaminophen doses at or above 1000 mg [2]. Lower doses did not seem to trigger respiratory reactions.