This review focuses on the latest advances in CLL therapy, particularly novel therapeutic targets under investigation such as CAR T-cell therapy, T-cell engagers, monoclonal antibodies, antibody–drug conjugates, and novel small molecule inhibitors, including BTK degraders, MALT1 inhibitors, c-MYC inhibitors, and CDK9 inhibitors. Here, MALT1 is linked to B-cell chronic lymphocytic leukemia.