Chronic rhinosinusitis (CRS) is an inflammatory sinonasal condition with multiple etiologic factors that is associated with a vast economic cost. Treatment is most frequently pharmacologic and has centered on agents that ameliorate inflammation, decrease bacterial or pathogen load, and facilitate egress of mucus or purulence from the sinonasal cavity. Nasal saline irrigations, topical nasal steroids, certain antibiotics, and systemic steroids have shown some efficacy in the management of CRS. Recently, biologic therapeutics that target specific inflammatory pathways associated with subsets of CRS have been developed and evaluated. Early data evaluating these biologic treatments suggest a potential role in treating a subset of CRS with refractory, poorly controlled disease. Additional studies are necessary to identify which patients would benefit most from biologic therapies and to assess the cost of these therapies compared with the benefit they provide. This review describes the pathophysiology of CRS and summarizes both established and novel biologic pharmacologic treatments.