The approvals of the Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib and more recently acalabrutinib as well as the B-cell lymphoma 2 (Bcl-2) antagonist venetoclax have transformed the treatment paradigm in both treatment-naïve and relapsed/refractory CLL [3,4,5,6,7,8,9,10,11,12]. The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.