The understanding and treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia have changed rapidly in the past 10 years. The outcome is equally as good as for Ph− disease, and with targeted tyrosine kinase inhibitor therapies in addition to chemotherapy, the novel immunotherapy approaches, and the extension of allogeneic hematopoietic stem cell transplant (allo-HCT) to older individuals, there is the potential to exceed this outcome. There is particular interest in reducing chemotherapy exposure and considering for whom allo-HCT can be avoided. However, the patient population that can help test these options in clinical trials is limited in number, and the available evidence is often derived from single-arm studies. This paper summarizes outcomes achieved with recent approaches to de novo Ph+ acute lymphoblastic leukemia in the postimatinib era and helps integrate all the available information to assist the reader to make informed choices for patients in an increasingly complex field.