Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are chronic conditions causing nasal inflammation. CRS is increasingly recognized as a chronic inflammatory process rather than a chronic infection. It is clinically classified based on the presence of nasal polyps into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While the primary initiating factors in CRS remain unclear, AR is driven by IgE mediated hypersensitivity to environmental allergens. Understanding the underlying inflammatory pathways and disease endotypes are driving innovation toward novel pharmacotherapies targeting critical mediators implicated in CRS and AR including IL-4, IL-13, IL-5, IgE, epithelial initiators IL-33 and TSLP. Many of these new agents have shown promise in RCTs or are being investigated in ongoing RCTs although none have approval for AR or CRS indications yet. Extensive investigations are still needed to determine the role, timing, predictive prognostic factors and long-term safety and efficacy of these agents.