A growing body of evidence shows that at least 40% of patients with unexplained (idiopathic) chronic urticaria have clinically relevant functional autoantibodies to the high-affinity IgE receptor on basophils and mast cells. The term "autoimmune urticaria" is used for this subgroup of patients presenting with continuous ordinary urticaria. Although immunoassays have been used in a research setting to screen sera for anti-FcεRI, there is a poor correlation between these results and in vitro functional histamine-release assays on basophils and cutaneous mast cells. Better laboratory assays need to be routinely available to clinicians to facilitate diagnosis. The simplest test of functional factors in the blood of patients with endogenous urticaria is the whealing response to intradermal injection with autologous serum, known as the ASST. Diagnosis of autoimmune urticaria hinges mainly on clinical suspicion in patients with the most severe presentations of chronic urticaria and without any other known cause or physical trigger. The use of immunotherapies may be helpful for patients with this pattern of severe refractory urticaria, especially when there is evidence of underlying autoimmunity or dependence on oral corticosteroid therapy for disease control.