Chronic rhinosinusitis (CRS) exhibits significant heterogeneity and has been generally classified as Type 1 (T1), T2, and T3 endotypes according to the histopathological and inflammatory features of the nasal mucosa. T2 inflammation has been regarded as the predominant endotype of CRS linked to disease severity and refractory conditions. The development of biological agents that specifically target key molecules involved in T2 inflammation offers a highly effective and promising therapeutic approach for CRS. Recent findings have expanded the understanding of CRS endotypes by incorporating a range of disease-related molecules for classification, with progress made on the endotyping of CRS without nasal polyps. In addition, there has been an increasing emphasis on the study of mixed inflammatory endotypes. This review examines recent findings on CRS endotyping and the related non-invasive biomarkers, as well as novel mechanisms governing endotype formation, and the efficacy of biologics in targeting T2 inflammation. Further research is warranted to understand if newly identified CRS endotypes show clinical significance for precision medicine and the management and treatment of refractory CRS in the era of biologics.