The therapeutic strategy in patients with Essential Thrombocythemia (ET) is a difficult balance between the prevention of bleeding and thrombotic complications and the risks of drug side effects and toxicity. Major bleeding is rare and seem to be related to higher platelet counts: therefore, a platelet count over 1500 x 10(9)/L is generally regarded as an indication for cytoreduction. Thrombotic complications include microvascular occlusive symptoms, which are reversible with low-dose aspirin, and large vessels thrombosis. The risk of major thrombosis is higher in ET patients aged more than 60 ys. and with previous occlusive event. In this high-risk group, the non-alkylating agent hydroxyurea (HU) significantly reduces the rate of vascular complications and has emerged as the treatment of choice. However, the long-term risk/benefit of HU remains disputed because its leukemogenic potential has not been ruled out. This holds also for other myelosuppressive agents, such as busulphan and pipobroman. Other drugs of particular interest for young patients include recombinant alpha-interferon (IFN) and Anagrelide. Both of them are effective in lowering platelet count, but their efficacy in reducing clinical complications remains to be demonstrated. However, both IFN and Anagrelide have shown to have frequent and clinically important side effects. Thus, further clinical studies are required to establish their role in the strategy of ET patient treatment.