In the last few decades, there has been a significant improvement in the prognosis of patients with acute leukemias. Still, the majority of patients succumb to these diseases. In recent years there has been a great surge in the understanding of the molecular mechanisms of disease which have provided us with new targets for anti-leukemia therapy. These range from chemotherapeutic agents with novel mechanisms of action, such as topoisomerase I inhibitors or demethylating agents, to reversal of drug-resistance mechanisms, to monoclonal antibodies directed against specific antigens, and targeted therapy that inhibit the function of molecules such as tyrosine kinases or Ras. The research on many of these agents is still in the early phases, but these new approaches offer the promise of finding a cure for the majority of patients with leukemia in the near future. Here we describe some of the promising approaches that are currently being investigated in the treatment of acute leukemias.