Allogeneic hematopoietic cell transplantation in first complete remission (CR1) is considered the standard of care, and the only established therapy that offers a possibility of cure for patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Unfortunately, a number of patients, with suitable HLA-matched donors, are unable to receive an allograft because they fail to respond, or relapse shortly after induction chemotherapy. Incorporating imatinib during the induction/consolidation phase is facilitating a higher number of potentially curative allografts by improving both remission rates and/or the durability of responses in patients with Ph+ ALL. Imatinib and other tyrosine kinase inhibitors are also improving outcomes in elderly patients with Ph+ ALL, ineligible for allografting, when combined with glucocorticoids, and/or conventional chemotherapy. The addition of imatinib or other tyrosine kinase inhibitors to the therapeutic armamentarium of Ph+ ALL is reshaping the treatment algorithm and improving prognosis of this dreadful disease.