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Ibrutinib is the first clinically approved inhibitor of Bruton’s tyrosine kinase, an enzyme that is essential for survival and proliferation of B‑cells by activating the B‑cell receptor signalling pathway. Ibrutinib has been shown to be highly effective in B‑cell malignancies in clinical trials and is recommended in current international guidelines as a first and/or second line treatment of chronic lymphocytic leukemia. The drug has a favorable tolerability and safety profile but the occurrence of specific side effects (e.g. atrial fibrillation, bleeding and hypertension) may complicate or be of concern for doctors and patients considering the use of this treatment. In many cases, however, it is not necessary to withhold this effective therapy. In contrast, ibrutinib treatment can be initiated or continued, if certain recommendations are followed. The possibilities of prevention, diagnosis and management of specific clinical situations are discussed in detail and recommendations are derived, which should facilitate ibrutinib use.