BACKGROUND Risk of anaphylaxis is included in the prescribing information for omalizumab, but the nature of these reactions merits further elaboration. OBJECTIVE To describe cases of anaphylaxis associated with omalizumab administration in patients with asthma. METHODS We reviewed spontaneous postmarketing adverse event reports submitted to the US Food and Drug Administration's Adverse Event Reporting System database and to the manufacturers of omalizumab and cases published in the literature through December 2006. Diagnostic criteria for anaphylaxis outlined by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network were used to screen cases. RESULTS One-hundred twenty-four cases of anaphylaxis associated with omalizumab administration in patients with asthma were identified. Many cases had a delayed onset of symptoms beyond 2 hours after dose administration. Many cases were also characterized by a protracted progression, with individual signs and symptoms of anaphylaxis staggered over hours. Review of the case reports did not reveal any predictive risk factors for the delayed onset or protracted progression of anaphylaxis. CONCLUSION Omalizumab-induced anaphylaxis may be characterized by a delayed onset and a protracted progression of symptoms. CLINICAL IMPLICATIONS The unusual timing of anaphylaxis in these cases challenges our understanding of anaphylaxis. A delayed onset of symptoms and protracted progression of anaphylaxis should be taken into account when administering omalizumab.