Chronic rhinosinusitis is a complex heterogeneous disease. Infection in the form of biofilm may have an important, if not central, role in the maintenance of the recalcitrant inflammation for this increasingly common chronic disease. Therefore, the importance of understanding the interaction of biofilm disease with the respiratory mucosa is imperative. Novel, minimally invasive methods of testing for the presence of this form of disease will need to become clinically accessible in order for equally innovative therapies to be widely applicable.