Venetoclax monotherapy has yielded disappointing results in acute myeloid leukemia (AML) because resistance develops along with the propagation of MCL1-expressing clones. Here, Marina Konopleva, MD, PhD, of the MD Anderson Cancer Center, Houston, TX, discusses different ways to inhibit MCL1 expression and overcome venetoclax resistance. These include direct MCL1 inhibition, MAPK inhibition, MDM2 inhibition, and CDK9 inhibition. Prof. Konopleva evaluates and compares these approaches. This video was recorded at the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, TX.