Clofarabine is a second-generation purine nucleoside analogue. It works mainly by inhibiting ribonucleotide reductase and incorporating into DNA. Clofarabine has shown efficacy in selected pediatric leukemias. It has also shown significant efficacy alone and in combination with other drugs in treating adult myeloid leukemias and high-risk myelodysplastic syndromes. Further, there is significant promise for clofarabine in the treatment of older patients with acute myeloid leukemia who are unlikely to benefit from standard induction chemotherapy due to unfavorable baseline prognostic factors. An oral formulation of clofarabine is also currently under development.