No curative treatment exists for MPN, possibly with the exception of allogeneic hematopoietic stem cell transplantation (HSCT), which is applicable only in a minority of patients. Currently, treatments for MPN are not very effective, or extremely costly. Hydroxyurea has been the standard of care for many decades. A reduction in thrombotic complications can be demonstrated in "high risk" MPN patients (age >60, presence of a previous thrombotic event), but hydroxyurea has no effect on the course of disease (no remission or substantial reduction of the mutant allele burden). Interferon alpha (IFNα) is a promising treatment for early stage PV and is currently being tested in phase III studies. However, IFNα is not always well tolerated and in phase II studies only a proportion of patients showed a substantial response. Ruxolitinib, recently approved for PMF with splenomegaly, is effective in reducing spleen size and improving quality of life, but has little effect on the JAK2-V617F mutant allele burden and has so far not been reported to induce remissions. Allogeneic HSCT is reserved for patients with PMF with a poor prognostic score. These including the recently developed JAK2 inhibitors reduce the symptoms of the disease, but, with the exception of pegylated interferon alpha (peg-IFNα), have little effect on the size of the neoplastic clone and are unable to induce molecular remissions. Thus, the percentage of mutant allele burden in hematopoietic cells does not change much even with successful treatment when considering symptom reduction. It is generally expected that reduction in the size of the malignant clone, as a surrogate marker of treatment success, will have the potential to reduce morbidity and result in prolonged survival of patients.