The BCR-ABL1–negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, can evolve into a form of secondary acute myeloid leukemia termed MPN in blast phase (MPN-BP). MPN in accelerated phase (MPN-AP), which is defined by 10% to 19% myeloid blasts in the peripheral blood or bone marrow, is a precursor to MPN-BP. Alternative definitions of MPN-AP exist based on studies identifying clinical variables that portend a poor prognosis and high risk for progression to MPN-BP. Allogeneic hematopoietic stem cell transplant remains the only curative therapeutic option; however, advanced age and high comorbidity index preclude the majority of patients from receiving this treatment modality. This article reviews management considerations for the advanced-phase MPNs (MPN-AP and MPN-BP), with a special focus on MPN-AP, and highlights novel experimental therapies.