Local activation of B cells and antibody production are important for protective and pathogenic immune responses. Furthermore, there is evidence that local activation of B cells and antibody production are important for pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and a severe subset of CRSwNP, aspirin-exacerbated respiratory disease (AERD). This review summarizes these findings and the potential role of B cells and antibodies in disease pathogenesis. Published literature from PubMed searches. Studies relevant to B cell development and the roles of B cells and antibodies in the pathogenesis of CRSwNP and AERD. Formation of tertiary lymphoid structures plays a key role in the local activation of B cells and antibody production. This process is important for fighting infections, but it also contributes to autoimmune disease. Furthermore, there is evidence to support a role for local B cell activation and antibody production in a variety of allergic diseases. Nasal polyp tissues from patients with CRSwNP and AERD have elevated levels of activated B cell subsets and locally produced antibodies. These locally produced antibodies may contribute to disease pathogenesis in a variety of ways, including activation of innate effector cells, whereas locally activated B cells may contribute to pathogenesis through the activation of T cells. More studies are needed to determine the role of B cells and antibodies in driving disease in these patients. However, targeting the processes that drive local B cell activation and antibody production may provide new therapeutic approaches and could help to reduce chronic inflammation.