ABSTRACT: Chronic urticaria remains a major problem in terms of etiology, investigation, and management. It is important to identify patients in whom physical urticaria is the principal cause of disability. Once confirmed by appropriate challenge testing, no further investigation is required. Urticarial vasculitis (UV) is a major differential diagnosis of "idiopathic" urticaria (CIU). I perform biopsy of most patients in this category because UV cannot be considered confirmed in the absence of histologic evidence. Patients with confirmed UV need to be thoroughly investigated for paraproteins, lupus erythematosus hepatitis B and C, and inflammatory bowel disease. Of patients with CIU, a few (<5%) prove to have food additive reactivity confirmed by placebo-controlled challenge testing. There is no convincing evidence of the involvement of Helicobacter pylori or parasite infestation as a cause of chronic urticaria, although H pylori could have an indirect role. Recently it has become clear that 27% to 50% of patients with CIU have functional autoantibodies directed against the alpha-chain of the high-affinity IgE receptor or less commonly against IgG. These antibodies, whose involvement has now been independently confirmed in several centers, are identified by autologous serum skin testing and confirmed by histamine release studies or immunoblotting. Their removal (by intravenous Ig or plasmapheresis) or treatment by cyclosporine has proved highly beneficial in severely affected patients. However, the routine treatment of all CIU patients, irrespective of etiology, remains the judicious use of H(1) antihistamines.