Go online to PeerView.com/AMC860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. It’s well known that the BTK inhibitor agent class is highly effective across several B-cell malignancies, including chronic lymphocytic leukemia and mantle cell lymphoma. Less well understood are the factors that can limit the effectiveness of covalent BTK inhibitors and the emerging strategies that can overcome therapeutic resistance and intolerance, which provide a new option for managing relapsed disease. In this animated, visually enhanced activity, a hematology-oncology expert outlines the clinically relevant mechanistic aspects of covalent and noncovalent BTK inhibitors, mechanisms and patterns of resistance to covalent agents, and rationale for integrating novel approaches to combatting resistance and intolerance. Upon completion of this CE activity, participants will be able to: Summarize the mechanistic and selectivity differences among covalent and noncovalent BTK inhibitors, including their implications for off-target effects, agent safety profiles, and therapeutic intolerance, Describe the mechanisms of BTK inhibitor resistance, including core mechanisms of acquired resistance to covalent agents and how noncovalent inhibitors can overcome resistance mutations.