To review the literature on the pathogenesis of chronic urticaria (excluding physical urticaria).PubMed was searched using the keywords urticaria and either chronic or autoimmune or pathogenesis for articles published from January 1972 to June 2007. All searches were limited to the English language. References from review articles on chronic urticaria were also considered for inclusion in this review.The authors selected relevant and current sources for inclusion in this review.No concise pathogenic mechanism has been identified for all cases of chronic urticaria, although evidence for a serologic mediator that may be autoimmune in nature has been identified in many cases. The activation of basophils and/or mast cells is a central feature in any theory proposed to explain this troubling disease.Further research is needed to better define the mechanism or mechanism(s) responsible for the development of chronic urticaria. Such research will lead to more effective and possibly even curative treatments.