Clinically, asthma and allergic rhinitis involve separate regions of the respiratory tract while representing a common underlying inflammatory syndrome. Much evidence supports an epidemiologic association between the diseases, paranasal sinus involvement in both conditions, and parallel relationship in severity and treatment outcomes. Pathophysiologic mechanisms, including immunoglobulin E (IgE)- mediated inflammation, are also shared. Blocking IgE with the recombinant humanized monoclonal antibody omalizumab demonstrated clinical efficacy in patients with upper and lower airway diseases. IgE blockade, leukotriene modulation, and B-cell depletion therapy have all exhibited success in chronic inflammation, reinforcing and expanding the beneficial role of immunomodulation of global mediators.