In the past few decades, the results of treatment for childhood acute lymphoblastic leukemia (ALL) have achieved about 80% long-term disease-free survival (DFS). Although the complete remission (CR) rate of adult ALL has also improved from 70 to 90%, 5-year overall survival (OS) remains only about 30% because of the high incidence of relapse. Especially, the disease with Philadelphia chromosome-positive (Ph+) ALL has been considered to have a poor prognosis. Recently, the selective inhibitor of BCR-ABL kinase, imatinib, showed significant efficacy in the treatment of Ph+ALL, and imatinib-combined chemotherapy for Ph+ALL is expected to improve the prognosis of this disease. At the same time, resistance to imatinib, resulting in relapse, is also reported. Once the patient relapses, subsequent cure becomes unlikely. The current available treatment to prevent recurrence of the disease is allogeneic hematopoietic transplantation (HST), if there is an HLA-matched donor. In Ph-negative (Ph-) ALL, young adults have superior outcomes with a 5-year OS of 81% when treated in pediatric clinical trials. HST may not always be necessary for this group of patients. For patients without donor or older than 50, novel biologic or targeted therapies are warranted, and early detection of minimal residual disease may also change strategies and improve the outcome of this disease.