This CME program discusses how Bruton’s tyrosine kinase inhibitors (BTKi) have improved treatment for chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and other B-cell malignancies. However, due to adverse events and treatment resistance, many patients discontinue treatment. A new generation of BTKi with a different mechanism of action (MOA) is emerging as a possible alternative. The program presents four modules that discuss the MOAs of covalent and non-covalent BTKi, current practices for using BTKi in treatment of CLL and MCL, the efficacy and safety data for novel BTKi, and the potential role of non-covalent BTKi in future treatment plans.