Chronic rhinosinusitis is one of the most common diseases among humans, affecting approximately 12% of the adult population globally. It is characterized by inflammation of the nasal cavity and sinuses, causing facial pressure and pain as well as long-term loss of smell. Benign masses called nasal polyps can also develop and cause chronic nasal obstruction, but the exact cause of this disease is unknown. Recent research has indicated that toxins produced by the bacterium Staphylococcus aureus, particularly enterotoxin B (SEB), may play an important role. SEB is thought to stimulate the immune system by activating proteins such as toll-like receptor 2 and pro-inflammatory cytokines and by causing reactive oxygen species production and endoplasmic reticulum stress. This inflammatory response may then disrupt the integrity of the epithelial cells in the nose and sinuses. Understanding these interactions between SEB and the immune system has led to the development of promising therapeutic agents such as dexamethasone, verapamil, and prostaglandin E2, but while many in vitro studies have been performed, the lack of suitable animal models has limited in vivo studies. Further research is thus needed to drive the development of new strategies for chronic rhinosinusitis prevention and treatment.