The nasal microbiome is altered in chronic rhinosinusitis (CRS), characterized by increased bacteria density and higher relative abundance of Staphylococcus aureus compared to healthy adults. This review examines determinants of S aureus nasal colonization, focusing on immune control and its evasion by the bacteria. CRS and asthma share pathomechanisms of chronic airway inflammation and often co-occur. In both conditions, many patients are sensitized to secreted factors of S aureus enterotoxins and serine protease-like proteins, and produce specific IgE, which influences the disease course. Therefore, we propose to incorporate S aureus –specific IgE measurements into the routine diagnostic evaluation of CRS and asthma.