Clinical data supporting the efficacy and safety of IFN-α, particularly pegylated formulations, in polycythemia vera, essential thrombocythemia, myelofibrosis, and chronic myeloid leukemia are reviewed, along with insights into next-generation IFNs and combination therapies. The gene discussed is IFNA17; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.