Inhibitor of Apoptosis (IAP) proteins exert essential functions during tumorigenesis as well as treatment resistance by simultaneously blocking cell death pathways and promoting cell survival. As IAP proteins are typically aberrantly expressed in human cancers including hematological malignancies, they represent in principle promising targets for therapeutic interventions. There are currently exciting opportunities to rationally exploit the therapeutic targeting of IAP proteins for the treatment of leukemia and lymphoma. Further insights into the signaling pathways that are under the control of IAP proteins and into the specific IAP protein-dependent vulnerabilities of hematological neoplasms are expected to pave the avenue to novel treatment strategies.