BACKGROUND: Chronic rhinosinusitis (CRS) is the downstream manifestation of heterogeneous pathophysiologic mechanisms leading to chronic sinonasal inflammation. Traditional grouping of patients by symptoms or clinical findings/phenotypes is being replaced by classification of CRS patients based on the underlying pathophysiologic mechanisms: endotypes. OBJECTIVE OF REVIEW: To provide an up-to-date review on the current knowledge of CRS endotypes with a focus on how the pathophysiologic mechanisms defined by each endotype may be targeted therapeutically. Special emphasis is placed on the clinical relevance of the material and how it may inform the current practice of otolaryngologists. TYPE OF REVIEW: A systematic review of contemporary literature review focusing on the latest studies examining the role of endotypes in the management and treatment of CRS. SEARCH STRATEGY: A MEDLINE and PubMed Central search were undertaken to perform this review using the keywords "Endotype" and "Sinusitis." EVALUATION METHOD: Articles containing the keywords, as well as the references of those articles, were then examined for relevance. RESULTS: The endotypes for CRS are often defined based on the balance of T-helper cell patterns of inflammation and can be grouped into Th2 and non-Th2 inflammation. These groups have shown a variable response to medical and surgical therapy, demonstrating that existing mainstream treatments can be tailored to patients with specific endotypes. The inflammatory mediators of Th2 inflammation, IL-4, IL-5 and IL-13 as well as IgE, are targeted by available biologic drugs that can be used for treatment of refractory disease. CONCLUSIONS: Increased understanding of CRS endotypes has led to the identification of biomarkers that define these endotypes and act as targets for potential therapeutics. Increasing knowledge about characteristics associated with these endotypes and their responses to treatments, including both established mainstream CRS treatments and novel biologic medications, has allowed incorporation of CRS endotypes into the current clinical decision-making. Treatment of CRS patients based on consideration of their endotypes is therefore not only presently possible but may improve clinical outcomes of those patients as well.