In this episode, Blood Associate Editor Dr. Jason Gotlib discusses the Review Series "The New Wave of Targeted Therapeutics for MPN’s", with authors Drs. Stefan Constantinescu, Ann Mullally, and Marina Kremyanskaya. This Review Series covers 3 areas where exciting advances are occurring. Dr. Constantinescu discusses “Next-generation JAK inhibitors in the treatment of myeloproliferative neoplasms” which describes how new ways to switch off JAK signaling are delivering a suite of new small-molecule drugs with potential. Dr. Mullally discusses “Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis” which reviews the biology of calreticulin mutations in myelofibrosis and ET and how multiple different modalities can be brought to bear against this mutant surface protein, including monoclonal antibodies, bispecific T-cell engagers, and cellular and vaccine therapies. Dr. Kremyanskaya discusses “Modulators of the hepcidin pathway in polycythemia vera and myelofibrosis” which outlines the major recent progress being made in controlling excessive erythropoiesis through pharmacological modulation of iron metabolism.