An increased understanding of cellular signaling pathways, like the JAK?STAT pathway, and the identification of the JAK2 V617F mutation in the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), has generated great interest in the development of targeted JAK2 inhibitors. In a recently completed Phase I?II study, ruxolitinib, a selective orally available JAK1 and JAK2 inhibitor, has shown efficacy in patients with advanced myelofibrosis. Constitutive activation of the JAK?STAT pathway has also been implicated in other hematological malignancies suggesting a potential role of JAK kinase inhibitors in these malignancies.This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of ruxolitinib. The literature for this article was retrieved from PubMed database searches using the keywords ?ruxolitinib?, ?INCB 018424?, ?JAK2 inhibitors? and ?leukemia?.The JAK?STAT signaling pathway plays a vital role in leukemogenesis. Ruxolitinib, a potent JAK1 and JAK2 inhibitor, known to decrease spleen size and alleviate constitutional symptoms in myelofibrosis, represents a potentially promising agent for the treatment of leukemias by inhibiting the JAK?STAT signaling. Further studies of ruxolitinib, in patients with acute and chronic leukemias, are now needed to establish the clinical usefulness of this promising drug.