AbstractChronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with eosinophilic tissue infiltration linked to type 2 inflammation and characterized by elevated levels of interleukin (IL)‐5 and other type 2 inflammatory mediators. Although distinct and overlapping contributions of eosinophils and IL‐5 to CRSwNP pathology are still being explored, they are both known to play an important role in NP inflammation. Eosinophils secrete numerous type 2 inflammatory mediators including granule proteins, enzymes, cytokines, chemokines, growth factors, lipids, and oxidative products. IL‐5 is critical for the differentiation, migration, activation, and survival of eosinophils but is also implicated in the biological functions of mast cells, basophils, innate lymphoid cells, B cells, and epithelial cells. Results from clinical trials of therapeutics that target type 2 inflammatory mediators (including but not limited to anti‐IL‐5, anti‐immunoglobulin‐E, and anti‐IL‐4/13) may provide further evidence of how eosinophils and IL‐5 contribute to CRSwNP. Finally, the association between eosinophilia/elevated IL‐5 and greater rates of NP recurrence after endoscopic sinus surgery (ESS) suggests that these mediators may have utility as biomarkers of NP recurrence in diagnosing and assessing the severity of CRSwNP. This review provides an overview of eosinophil and IL‐5 biology and explores the literature regarding the role of these mediators in CRSwNP pathogenesis and NP recurrence following ESS. Based on current published evidence, we suggest that although eosinophils play a key role in CRSwNP pathophysiology, IL‐5, a cytokine that activates these cells, also represents a pertinent and effective treatment target in patients with CRSwNP.