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 alone. 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 T-cell precursors. Traditional risk stratification has been based on clinical factors such as age, white blood cell count, and response to chemotherapy, but the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, multi-agent chemotherapy remains the backbone of therapy, with allogeneic stem cell transplantation (Allo-SCT) for eligible candidates. Elderly patients often cannot tolerate such regimens and have a particularly poor prognosis. Recent advances in treatment include the use of targeted therapies, such as tyrosine kinase inhibitors (TKIs) for Ph-like ALL, and novel monoclonal antibodies like blinatumomab for relapsed/refractory disease. The National Comprehensive Cancer Network (NCCN) has developed recommendations for risk stratification, considering age, white blood cell count, and cytogenetic changes. Treatment options for relapsed/refractory ALL include augmented cytotoxic chemotherapy, reformulated single-agent chemotherapy, and novel monoclonal antibodies. Future therapies may include monoclonal antibodies targeting CD22, CD20, CD19, and CD25, as well as proteasome inhibitors, JAK inhibitors, hypomethylating agents, PI3K/mTOR inhibitors, and chimeric antigen receptor (CAR) T cells.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 alone. 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 T-cell precursors. Traditional risk stratification has been based on clinical factors such as age, white blood cell count, and response to chemotherapy, but the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, multi-agent chemotherapy remains the backbone of therapy, with allogeneic stem cell transplantation (Allo-SCT) for eligible candidates. Elderly patients often cannot tolerate such regimens and have a particularly poor prognosis. Recent advances in treatment include the use of targeted therapies, such as tyrosine kinase inhibitors (TKIs) for Ph-like ALL, and novel monoclonal antibodies like blinatumomab for relapsed/refractory disease. The National Comprehensive Cancer Network (NCCN) has developed recommendations for risk stratification, considering age, white blood cell count, and cytogenetic changes. Treatment options for relapsed/refractory ALL include augmented cytotoxic chemotherapy, reformulated single-agent chemotherapy, and novel monoclonal antibodies. Future therapies may include monoclonal antibodies targeting CD22, CD20, CD19, and CD25, as well as proteasome inhibitors, JAK inhibitors, hypomethylating agents, PI3K/mTOR inhibitors, and chimeric antigen receptor (CAR) T cells.