Chronic urticaria includes several different subsets with distinct pathophysiologies, and with important implications for investigation and treatment. Chronic 'idiopathic' urticaria represents a special challenge, which, until recently, was not taken up by dermatological or immunological investigators. However, it has now emerged that at least 30% of patients possess histamine-releasing autoantibodies against Fc epsilon R1, or less commonly IgE itself. These autoantibodies are causative. Recent work implicates complement activation in most cases. Functional (i.e. histamine releasing) autoantibodies are specific to chronic urticaria. However, immunoreactive (non-histamine-releasing) anti-Fc epsilon R1 autoantibodies can be found in sera of patients with physical urticarias and with autoimmune connective tissue and bullous diseases. The reason for the occurrence of this disease type in some individuals but not others is unclear. One possibility is the development, in genetically predisposed persons, of autoantibodies by molecular mimicry - perhaps against lipopolysaccharide of Helicobacter pylori, an organism frequently infecting the upper gastrointestinal tract of chronic urticaria patients.