Second-generation antihistamines are considered first-line agents in the treatment of chronic urticaria because of their safety and efficacy profile. Some patients require higher doses of H₁ antihistamines alone or in combination with other classes of medications, including H₂ antihistamines, leukotriene receptor antagonists, or first-generation H₁ antihistamines. One major therapeutic advance has been omalizumab, a humanized monoclonal anti–immunoglobulin E that was recently approved by the US Food and Drug Administration for the treatment of chronic urticaria that is unresponsive to H₁ antagonists. In addition, the second article in this continuing medical education series outlines several evidence-based alternative treatments for urticaria and the differences in recommendations between 2 major consensus groups (the European Academy of Allergy and Clinical Immunology/World Allergy Organization and the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force).