Summary: Chronic spontaneous urticaria (CSU) is a long-standing inflammatory condition of the skin and mucus membranes resulting in significant quality of life impairment. The typical signs and symptoms of CSU comprise hives, pruritus and/or angioedema which develop daily or on most days of the week for longer than 6 weeks. Antihistamines in up to 4-fold of the standard dose are the drugs of choice in CSU and in the treatment refractory cases anti-IgE monoclonal antibody (omalizumab) or immunosuppressant (ciclosporine) are recommended. Up to one third of patients suffering from CSU do not achieve urticaria resolution despite receiving a combination of the above mentioned treatments. Moreover, antihistamines use is often associated with burdensome side effects i.e. drowsiness or sedation disrupting daily activity and limiting educational/work productivity which compromises therapy adherence even in the treatment-responsive cases. Omalizumab accessibility is limited due to its high price and subcutaneous route of administration while ciclosporine lacks approval for CSU treatment, its safety profile raises some concerns as for chronic use in CSU, too. Increasing understanding of the role of mast cells, basophils and B cells in hives and angioedema formation paved the way to the emerging concept of using Bruton’s tyrosine kinase inhibitors (BTKi) in CSU as their mechanism of action carries the potential to inhibit all of the key players in CSu inflammatory cascade. Heretofore, BTKi have been associated mainly with hematologic disorders, its introduction to the market in 2013 in mantle cell lymphoma treatment revolutionized management of B cell-line originating malignancies. Besides spectacular efficacy, BTKis major advantage is oral route of administration. However, the type, incidence rate and severity of the classic BTKis side effects (i.e. thrombocytopenia, heart rhythm disturbances, risk of infection) limit their use outside oncologic setting. The development of novel BTKi with substantially improved safety profile greatly increases range of their possible indications, with special focus on autoimmune disorders, including CSU. In line with that, three novel BTKis – remibrutinib, fenibrutinib and rilzabrutinib - are in the advanced stages of phase II and III clinical trials in CSU patients and the recently released results are promising enough to hope that BTKis carry the potential to fill in the gap in CSU treatment.