While the U.S. Food and Drug Administration (FDA) has approved immunotherapies including monoclonal antibodies with/without drug conjugates, bispecific T‑cell engager (BiTE), immune checkpoint inhibitors and chimeric antigen receptor T cells (CAR-T) for lymphoid neoplasms which have dramatically improved the survival of patients with lymphoma, acute lymphoblastic leukemia and multiple myeloma; approval of immunotherapies for myeloid malignancies has lagged. After the approval, withdrawal and eventual re-approval of the CD33 antibody-drug conjugate, gemtuzumab ozogamicin, for the treatment of CD33-positive acute myeloid leukemia (AML) in 2017 and the approval of the CD123- binding drug conjugate, tagraxofusp-erzs, for the treatment of the patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in 2018, no other immunotherapies have achieved regulatory approval for myeloid neoplasms. Until now, success in myeloid neoplasms has come from targeting mechanisms of survival and specific mutations. In this context, the promising data and novel approaches described in the past years lead us now to ask if immunotherapies for myeloid neoplasms are finally ready for prime time. This session will discuss the promising data from these novel approaches and explore the potential of immunotherapies in myeloid neoplasms. Dr. Sarit Assouline will discuss the potential of BiTEs, immune checkpoint molecules, macrophage checkpoint molecules for AML and high-risk MDS. Dr. Saar Gill will address the barriers of CAR-T therapy for high-grade myeloid neoplasms and provide strategies to overcome these barriers.