Chronic rhinosinusitis with nasal polyps often represents a chronic severe inflammatory disease of the upper airways. Nasal polyps (chronic rhinosinusitis with nasal polyps) are characterized by a T-helper-2 dominated cytokine pattern including high interleukin-5 while chronic rhinosinusitis without polyps exhibits T-helper-1 biased cytokine releas with high IFN-gamma concentrations. S. aureus derived enterotoxins function as superantigens and in nasal polyps a significant higher colonisation and immune response to enterotoxins has been found. Furthermore, S. aureus derived enterotoxins influence local immunoglobulin synthesis and induce polyclonal immunoglobulin E production, which may contribute to severe inflammation via activation of mast cells. From this new understanding of chronic rhinosinusitis with nasal polyps, new therapeutic approaches emerge such as anti-interleukin-5, anti-immunoglobulin E, and antibiotic treatment. These may enlarge the nonsurgical armentarium. Furthermore more evidence is now available that this model of disease modification by superantigens is also applicable to lower airway diseases like late-onset asthma.