Availability of novel inhibitors of B-cell receptor signaling (BCR, Bruton’s tyrosine kinase [BTKi] [1] or phosphatidylinositol 3-kinase [PI3ki]) [2] or B-cell lymphoma-2 (BCL2i) [3] has transformed the treatment landscape for treatment-naïve (TN) and relapsed/refractory (RR) CLL. The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.