The treatment landscape of chronic lymphocytic leukemia (CLL) has significantly changed in the last few years thanks to the discovery of targeted drugs directed against pivotal kinases, such as BTK [ibrutinib (IB), acalabrutinib, zanubrutinib, and pirtobrutinib] or PI3K (idelalisib and duvelisib), anti-apoptotic protein, such as BCL2 (venetoclax), and new monoclonal antibodies targeting CD19 (tafasitamab) or CD20 (1–3). This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.