Despite a prolonged survival of around 15 years linked to a prolonged complete remission induced by myelosuppression, myeloproliferative syndromes such as polycythemia vera (PV) and essential thrombosis (ET) remain at risk of lethal adverse affects such as thrombotic events and acute transformation. The major risk at diagnosis, in the absence of treatment, is essentially thrombosis. Different therapeutic trials have shown the necessity to maintain circulating blood cells (RBC and platelets counts) near normal levels to avoid thrombosis. Phlebotomies alone in PV lead in the long run to metaplasia and increased platelet counts and should only be kept for emergency cell count reduction. Myelosuppression is thus until recently the most widely accepted effective alternative. However, the effects of long term chronic administration of myelosuppresive agents needs to be analyzed and monitored as the biological changes which appear during the course of these diseases linked or not to the intrinsic clonal haematopoietic abnormality may lead to malignant transformation. Thus, alternative therapies need to be evaluated and predisposition factors taken in account.