Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has historically been associated with poor prognosis and limited therapeutic options. Over the past two decades, however, the treatment paradigm has markedly shifted. The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and ponatinib, has revolutionized frontline therapy, significantly improving remission rates and long-term survival. These agents, when combined with reduced-intensity chemotherapy or even with corticosteroids, have enabled less toxic regimens, particularly beneficial for older or unfit patients. The implementation of measurable residual disease (MRD) monitoring has emerged as a pivotal tool for risk stratification and therapeutic decision-making. Consequently, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), considered a cornerstone of curative treatment, is being re-evaluated in patients achieving sustained deep molecular responses. More recently, immunotherapeutic strategies-including the bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR) T-cell therapies-have emerged as effective alternatives to conventional chemotherapy and TKIs. This review outlines the major advances in the management of Ph+ ALL, emphasizing the move toward more personalized, targeted, and less toxic treatment approaches.