Acute lymphoblastic leukemia is a heterogeneous disease with distinct biologic and prognostic groupings. Although current therapies result in high complete remission rates, long-term disease-free survival rates have remained disappointingly low. Results from recent studies using risk-tailored approaches suggest improvement in overall survival for high-risk groups, such as those with Philadelphia chromosome-positive acute lymphoblastic leukemia. Furthermore, the incorporation of imatinib mesylate into the treatment regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia patients may lead to better outcomes. Finally, quantification of minimal residual disease at various time points during therapy is being investigated as a means to predict more accurately a patient's response to therapy, and to make therapeutic decisions.