Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from B-cell precursors, while the remainder are from T-cell precursors. Traditional risk stratification is based on clinical factors such as white blood cell count and response to chemotherapy, but the identification of recurrent genetic alterations has helped refine prognosis and guide management. Despite advances in treatment, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids, and an anthracycline, with allogeneic stem cell transplantation for eligible candidates. Elderly patients often cannot tolerate these regimens and have a poor prognosis. Recent advances in treatment include the use of kinase inhibitors for Ph-like ALL, which has a worse prognosis than Ph-positive ALL. The National Comprehensive Cancer Network (NCCN) has developed recommendations for risk stratification in adult ALL. The treatment of adult ALL has been adapted from pediatric protocols, but success rates are much lower in adults. Chemotherapy consists of induction, consolidation, and long-term maintenance, with CNS prophylaxis given throughout therapy. The backbone of induction therapy typically includes vincristine, corticosteroids, and an anthracycline. The Hyper-CVAD/Methotrexate-cytarabine regimen is an alternative approach. Special consideration is needed for Ph-positive ALL, which has a poor prognosis. The advent of TKIs has improved survival for Ph-positive ALL. Blinatumomab, a bispecific anti-T-cell receptor/anti-CD19 antibody, has shown promise in treating relapsed/refractory ALL. Nelarabine is a T-cell specific purine nucleoside analog approved for relapsed/refractory T-cell ALL. Monoclonal antibodies targeting CD22 and CD19 have shown activity in treating ALL. Proteasome inhibitors, JAK inhibitors, and hypomethylating agents are also being explored as potential treatments. CAR-T cell therapy is a promising new approach for treating ALL. These advances have significantly improved outcomes for patients with ALL.Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from B-cell precursors, while the remainder are from T-cell precursors. Traditional risk stratification is based on clinical factors such as white blood cell count and response to chemotherapy, but the identification of recurrent genetic alterations has helped refine prognosis and guide management. Despite advances in treatment, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids, and an anthracycline, with allogeneic stem cell transplantation for eligible candidates. Elderly patients often cannot tolerate these regimens and have a poor prognosis. Recent advances in treatment include the use of kinase inhibitors for Ph-like ALL, which has a worse prognosis than Ph-positive ALL. The National Comprehensive Cancer Network (NCCN) has developed recommendations for risk stratification in adult ALL. The treatment of adult ALL has been adapted from pediatric protocols, but success rates are much lower in adults. Chemotherapy consists of induction, consolidation, and long-term maintenance, with CNS prophylaxis given throughout therapy. The backbone of induction therapy typically includes vincristine, corticosteroids, and an anthracycline. The Hyper-CVAD/Methotrexate-cytarabine regimen is an alternative approach. Special consideration is needed for Ph-positive ALL, which has a poor prognosis. The advent of TKIs has improved survival for Ph-positive ALL. Blinatumomab, a bispecific anti-T-cell receptor/anti-CD19 antibody, has shown promise in treating relapsed/refractory ALL. Nelarabine is a T-cell specific purine nucleoside analog approved for relapsed/refractory T-cell ALL. Monoclonal antibodies targeting CD22 and CD19 have shown activity in treating ALL. Proteasome inhibitors, JAK inhibitors, and hypomethylating agents are also being explored as potential treatments. CAR-T cell therapy is a promising new approach for treating ALL. These advances have significantly improved outcomes for patients with ALL.