Sameem M Abedin,1 Craig S Boddy,1 Hidayatullah G Munshi1–3 1Department of Medicine, Feinberg School of Medicine, Northwestern University, 2Medicine Service, Jesse Brown VA Medical Center, 3The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA Abstract: The bromodomain and extra-terminal (BET) family of proteins are important epigenetic regulators involved in promoting gene expression of critical oncogenes. BET inhibitors have been demonstrated to repress c-Myc expression, and were initially shown to have efficacy in a number of c-Myc-dependent hematologic malignancies. Recent studies have now revealed a broader role for BET inhibitors in hematologic malignancies. In this review, we summarize the efficacy of BET inhibitors in preclinical models of acute leukemia, lymphoma, and multiple myeloma. We also summarize recent results of clinical trials utilizing BET inhibitors in hematologic malignancies, characterize potential resistance mechanisms to BET inhibitors, and discuss potential combination therapies with BET inhibitors in patients with hematologic malignancies. Keywords: leukemia, lymphoma, multiple myeloma, toxicity, resistance mechanisms