When rhinosinusitis - the inflammation of the nasal cavity and paranasal sinuses - persists for over 12 weeks, it is termed 'chronic rhinosinusitis' (CRS). Both innate and adaptive immunity contribute to the heterogeneous inflammatory pathogenesis of CRS, which is driven by genetic and environmental factors and the microbiome. CRS is classified by the presence of polyps. Molecular mechanisms in CRS with nasal polyps are similar to those in atopic diseases. Areas covered: This review focuses on the immune pathogenesis of CRS, differences between the two CRS subtypes, and latest treatments that may aid in the provision of personalized medicine. Expert opinion: Basic research in the last decade has helped significantly in enhancing our knowledge of the pathophysiologic processes of CRS, due to which there is now a better understanding of the associated natural history, physiopathology, novel treatments, and prevention strategies. Treatment success depends on the clarification of the underlying pathogenesis and disease-contributing factors. The exploration of disease endotypes and introduction of novel agents are important advancements. Prior studies performed without disease-endotyping resulted in the inefficiency of certain drugs and insignificant results. The identification of biomarkers, development of personalized approaches, and utilization of disease algorithms are required for CRS therapy success.