Chronic rhinosinusitis (CRS) has been differentiated clinically into CRS without nasal polyps and CRS with nasal polyps, with both forms subjected to glucocorticosteroid and antibiotic treatments and, if not successful, to nasal and sinus surgery tailored to endoscopic and computed tomographic scan findings. The elaboration of endotypes based on pathomechanisms involving different immune responses offers new possibilities in terms of prediction of prognosis and risks and sophisticated guidance in personalized pharmacotherapy, surgical approaches, and innovative treatment approaches in the CRS field with various biologics. Surgical approaches can vary from classical functional endoscopic sinus surgery to extended and "reboot" approaches, with the idea to completely remove the dysfunctional and inflamed mucosa and replace it with a newly grown healthy mucosa. Biologics in this field are targeting the type 2 cytokines IL-4, IL-5, and IL-13, as well as IgE. Phase I and II study results are promising, and phase III studies are currently being performed. The development of endotype-driven integrated care pathways appreciating these innovations are now needed for the management of CRS.