Acute lymphoblastic leukemia (ALL) in children has seen remarkable improvements in treatment outcomes, with approximately 80% of children being cured. These advancements stem from intensive multiagent chemotherapy, identification of predictive clinical and biological variables, supportive care improvements, and large-scale clinical trials. Despite this success, challenges remain, including better treatment for relapsed patients, less toxic therapies, and managing late effects of treatment. ALL is the most common childhood cancer, accounting for nearly 25% of all childhood cancers and 72% of pediatric leukemia cases. It occurs at a rate of 3-4 cases per 100,000 children under 15 years. Incidence peaks in children aged 2-5 years, with males more affected than females, except in infants. Geographic variations exist, with higher incidence in industrialized Western countries. Maternal reproductive history and in utero growth factors are linked to ALL risk. Genetic factors, such as ARID5B and IKZF, and environmental factors like radiation and chemicals, also play roles. ALL results from complex interactions between genetic and environmental factors. Genetic abnormalities, such as the (4,11) translocation and MLL-AF4 fusion gene, are associated with high concordance rates. Familial cases and chromosomal abnormalities like Down syndrome increase ALL risk. Viral infections and immunodeficiencies may also contribute. ALL is classified based on morphology, immunophenotype, and genetics. The World Health Organization (WHO) classification divides ALL into precursor B-cell, precursor T-cell, and mature B-cell ALL. Immunophenotypic classification is now preferred over the older FAB classification. Clinical presentation includes bone marrow infiltration, anemia, thrombocytopenia, neutropenia, and bone pain. Laboratory findings often show elevated white blood cell counts, anemia, and thrombocytopenia. Bone marrow aspiration is essential for diagnosis. Prognostic factors include age, initial white blood cell count, immunophenotype, and cytogenetics. Early response to therapy and minimal residual disease (MRD) levels are critical for prognosis. Risk groups are divided into standard, intermediate, and high-risk. Treatment involves induction therapy, early intensification, consolidation, delayed intensification, and maintenance therapy. HSCT is considered for high-risk or relapsed cases. Relapsed ALL is less responsive and requires more intensive treatment. Outcomes have improved significantly, with over 95% of children achieving remission and approximately 80% being long-term survivors. Survival rates vary by risk category, with infant leukemia having the worst outcomes. HSCT is crucial for high-risk patients, particularly those with MLL-rearranged ALL or poor early responses. Novel therapies, including clofarabine and imatinib, are being explored to improve outcomes for relapsed/refractory ALL. These agents target specific signaling pathways and offer potential forAcute lymphoblastic leukemia (ALL) in children has seen remarkable improvements in treatment outcomes, with approximately 80% of children being cured. These advancements stem from intensive multiagent chemotherapy, identification of predictive clinical and biological variables, supportive care improvements, and large-scale clinical trials. Despite this success, challenges remain, including better treatment for relapsed patients, less toxic therapies, and managing late effects of treatment. ALL is the most common childhood cancer, accounting for nearly 25% of all childhood cancers and 72% of pediatric leukemia cases. It occurs at a rate of 3-4 cases per 100,000 children under 15 years. Incidence peaks in children aged 2-5 years, with males more affected than females, except in infants. Geographic variations exist, with higher incidence in industrialized Western countries. Maternal reproductive history and in utero growth factors are linked to ALL risk. Genetic factors, such as ARID5B and IKZF, and environmental factors like radiation and chemicals, also play roles. ALL results from complex interactions between genetic and environmental factors. Genetic abnormalities, such as the (4,11) translocation and MLL-AF4 fusion gene, are associated with high concordance rates. Familial cases and chromosomal abnormalities like Down syndrome increase ALL risk. Viral infections and immunodeficiencies may also contribute. ALL is classified based on morphology, immunophenotype, and genetics. The World Health Organization (WHO) classification divides ALL into precursor B-cell, precursor T-cell, and mature B-cell ALL. Immunophenotypic classification is now preferred over the older FAB classification. Clinical presentation includes bone marrow infiltration, anemia, thrombocytopenia, neutropenia, and bone pain. Laboratory findings often show elevated white blood cell counts, anemia, and thrombocytopenia. Bone marrow aspiration is essential for diagnosis. Prognostic factors include age, initial white blood cell count, immunophenotype, and cytogenetics. Early response to therapy and minimal residual disease (MRD) levels are critical for prognosis. Risk groups are divided into standard, intermediate, and high-risk. Treatment involves induction therapy, early intensification, consolidation, delayed intensification, and maintenance therapy. HSCT is considered for high-risk or relapsed cases. Relapsed ALL is less responsive and requires more intensive treatment. Outcomes have improved significantly, with over 95% of children achieving remission and approximately 80% being long-term survivors. Survival rates vary by risk category, with infant leukemia having the worst outcomes. HSCT is crucial for high-risk patients, particularly those with MLL-rearranged ALL or poor early responses. Novel therapies, including clofarabine and imatinib, are being explored to improve outcomes for relapsed/refractory ALL. These agents target specific signaling pathways and offer potential for