Allergen-specific immunotherapy (SIT) is the only causal treatment of allergic disorders and therefore a cornerstone in the management of respiratory allergy. SIT is effective in patients with allergic rhinitis and mild-to-moderate allergic asthma. Successful treatment is associated with decrease in allergic symptoms of the upper and lower airways. The most relevant limitation in the daily routine is the restricted use of SIT in patients with moderate-to-severe allergic asthma. A strategy to overcome this limitation is to combine SIT with immunmodulators. One example of a recently developed immunmodulator is Omalizumab, a humanized, monoclonal anti-IgE antibody that binds to circulating IgE molecules, thus interrupting the allergic cascade downstream the IgE production of B cells. Up to now, four clinical trials have been performed, which all showed that the combination of Omalizumab and SIT is safe and clinically more effective than SIT alone. Moreover, administration of Omalizumab prior to SIT reduces the risk of SIT-related systemic reactions. Omalizumab and SIT are also effective in patients with mild-moderate allergic asthma. In conclusion, the use of Omalizumab as an additive immunmodulator improves safety and efficacy and might be a useful approach to broaden the indication of specific immunotherapy in allergic patients.