In the last 2 decades, an increasing understanding of pathophysiological mechanisms in chronic rhinosinusitis (CRS) opened an avenue from phenotyping to endotyping, from eosinophilic inflammation to type 2 immunity, and from the ventilation and drainage paradigm to the mucosal concept for therapeutic considerations. With the advent of type 2 endotyping and targeted biomarkers, precise endotype-driven therapeutic options are possible including biologics and adapted surgical approaches. We here aim to focus on the complexity and heterogeneity of the features of CRS endotypes, especially for those with nasal polyps, including its history, latest developments, clinical associations, and endotype-driven solutions. In order to better manage uncontrolled severe CRS in clinical practice, medical decisions based on a profound understanding of the pathology and immunology of this heterogeneous disease, aiding a precision-medicine based approach for patient's treatment, are pivotal.