Thrombocytosis is a common clinical problem and it represents either a primary myeloid disorder (a clonal process) or a reactive phenomenon. While reactive thrombocytosis is often inconsequential, clonal thrombocytosis may require cytoreductive therapy to prevent thrombohemorrhagic complications. In this regard, a controlled clinical trial has previously demonstrated the efficacy of hydroxyurea in reducing the risk of thrombosis in high-risk patients with essential thrombocythemia (ET). Despite the absence of similar evidence for clinical benefit, the platelet-lowering agent anagrelide has been widely used in both ET and polycythemia vera (PV) and recent reports of serious side-effects suggest that such practice might be detrimental to patients. In the current review we provide basic drug information as well as a critical assessment of anagrelide treatment in ET and related disorders.