Cholinergic urticaria is one of the more common physical urticarias. Although it is often fairly mild, severe treatment-resistant disease may occur, with significant associated disability. Omalizumab, a monoclonal IgG anti-IgE antibody licensed for use in severe asthma, has recently been used successfully in several types of urticaria, including in one case of cholinergic urticaria. This paper reports a patient with severe cholinergic urticaria, unresponsive to antihistamines and multiple other treatments, whose disease was also unresponsive to omalizumab.