Clofarabine, a next-generation deoxyadenosine analog, has demonstrated significant activity in patients with acute myeloid leukemia (AML). The single-agent activity compares favorably with that demonstrated by the current standard antileukemia agents. Clofarabine has been safely and effectively combined with other agents and will probably become an integral part of induction and/or consolidation regimens in AML. Current studies are underway to better define the role of clofarabine in younger and elderly patients with AML, and also explore development strategies for an oral formulation.