New developments in the field of allergy and immunology have yielded a variety of novel therapeutic approaches in recent years, and more agents are at the clinical trial stage. Among the therapeutic approaches discussed in this review are Toll-like receptor agonists, immunostimulatory oligodeoxynucleotides, orally and parenterally administered cytokine blockers, and specific cytokine receptor antagonists. Transcription factor modulators targeting syk kinase, peroxisome proliferator-activated receptor-γ, and nuclear factor-κB are also being evaluated in the treatment of asthma. The anti-IgE monoclonal antibody omalizumab has established effectiveness in patients with allergic asthma, but the criteria for selecting patients who are most likely to benefit from it are less clear. This review summarizes data from human clinical trials with immunomodulators to discuss the rationale for their use, their efficacy, and adverse events associated with them.