Chronic urticaria (CU) is a disease characterized by pruritic weals, angio-oedema or both occurring for at least 6 weeks. It encompasses spontaneous and inducible urticarias. The national and international guidelines outline the principles of treatment. Omalizumab, an anti-immunoglobulin E monoclonal antibody, has transformed the management of many severe and treatment-refractory patients. However, current UK guidance on its use does not address the needs of those with less severe disease, inducible urticarias, idiopathic histaminergic angio-oedema without weals as a presentation of CU and omalizumab non-responders. Our algorithm and a summary of the evidence to support its principles offers guidance and a more systematic targeted approach to using a range of 'off-label' agents for specific phenotypes of CU. It will be of use when guideline-recommended mast cell mediator antagonists fail to control symptoms and/or using omalizumab is ineffective, not practical or unfunded.