Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend 
the use of the IgE-targeted biologic omalizumab in patients with 
antihistamine-refractory disease. The rationale for this is supported by the key 
role of IgE and its high-affinity receptor, FcεRI, in the degranulation of skin 
mast cells that drives the development of the signs and symptoms of CSU, itchy 
wheals, and angioedema. Here, we review the current understanding of the 
pathogenesis of CSU and its autoimmune endotypes. We describe the mechanisms of 
action of omalizumab, the only biologic currently approved for CSU, its efficacy 
and ways to improve it, biomarkers for treatment response, and strategies for 
its discontinuation. We provide information on the effects of the off-label use, 
in CSU, of biologics licensed for the treatment of other diseases, including 
dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we 
discuss targets for novel biologics and where we stand with their clinical 
development. These include IgE/ligelizumab, IgE/GI-310, thymic stromal 
lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like 
lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide 
updated information and guidance on the use of biologics in the treatment of 
patients with CSU, now and in the near future.