Chronic rhinosinusitis (CRS) is a highly prevalent disease in the adult and pediatric population. It causes significant burden and the management is considered one of the most costly public health conditions. Comorbidities include asthma, aspirin sensitivity, and nasal polyposis. Staphylococcus aureus biofilms and exotoxins that act as superantigens have been implicated to play an important pathological role in the incidence, maintenance, and ongoing burden of CRS. A better understanding of the interplay between bacterial factors, host factors, and the environment will facilitate better management of this disease. This literature review focuses on these factors and highlights current research in this field.