Innovation refers to the introduction of a product, a process, a service or a solution resulting in something new or significantly improved compared to the already available alternatives. In the clinical context, it is strictly related to the identification of a new added value in terms of quality, therapeutic efficacy and safety. Over the years several innovative approaches have been introduced in the clinical practice, revolutionizing the treatment and the management of important rhinologic conditions. Innovative tools, including new drugs, biomaterials, and mobile applications seem to be able to improve the clinical outcomes and the quality of life of many patients affected by (often relapsing) rhinologic diseases. Among the main modern pharmacological innovations, mention must be made of the biological drugs like monoclonal antibodies (mAbs). Recently, new mAbs have been introduced and investigated as useful arms in the treatment of some inflammatory/infectious or oncological diseases affecting the nasal cavities and paranasal sinuses. The already approved or still investigated mAbs work inhibiting different type 2 inflammation pathways, including those mediated by IgE (omalizumab), IL-4/IL-13 (dupilumab), and IL-5 (mepolizumab). Moreover, considering the higher expression of PD-L1 in nasopharyngeal carcinoma, the use of PD-1 inhibitors, such as nivolumab, or a dual CTLA-4/PD-1 blockade (ipilimumab plus nivolumab) appear to be an effective strategy for the treatment of this cancer form. The implants with bio-absorbable biomaterials represent new interesting available technological innovations. Moreover, advanced technologies such as the artificial intelligence, the machine learning as well as the augmented or virtual reality have also proved useful in rhinologic field with main impacts on precision medicine and surgery. Finally, the development and use of mobile-Health tools represent a winning strategy in monitoring of the therapy success, safety and tolerability as well as the progress of chronic disease including chronic rhinosinusitis with nasal polyps. Supporting the research of innovative tools and strategies (including pharmacological, technologic, or digital ones) is essential to improve the management of chronic diseases that significantly affect the patients' quality of life.