Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a chronic inflammatory disorder of the respiratory tract. It occurs in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), whose symptoms are exacerbated by strong cyclooxygenase 1 (COX-1) inhibitors. The fundamental pathomechanism of N-ERD is the dysregulation of arachidonic acid metabolism, leading to constant overproduction of the proinflammatory and bronchoconstrictor cysteinyl leukotrienes (LTs) and prostaglandin D2 (PGD2), along with the underproduction of the anti-inflammatory mediators, including prostaglandin E2 (PGE2). These biochemical disturbances are further exacerbated by the use of aspirin and other COX-1 inhibitors and are responsible for the typical clinical symptoms. Because many N-ERD patients have severe asthma and troublesome CRSwNP, they are good candidates for treatment with biologics. In this review paper the latest results of the research on the impact of biologics on the pathomechanisms of N-ERD and potential restoration of aspirin tolerance are presented.