Leukemia remains the most common cancer in childhood, and while great strides have been made in increasing event-free survival in the past 20 years, patients with high-risk features still pose a challenge for successful disease-free survival. Older children and adolescents are included in that high-risk group. Approximately 80-85% of cases of leukemia in the pediatric population are of the lymphocytic subtype. Overall disease-free survival rates for acute lymphocytic leukemia have increased to 80% for those with standard or low-risk disease and 65-70% for those with high-risk disease. This is a product of both a better understanding of the molecular pathophysiology of ALL and the development of better treatment strategies based on risk. In acute myelogenous leukemia, we have not achieved such success, and disease-free survival rates are in the 30-40% range. This article discusses the diagnosis of leukemia in the adolescent population with attention to pathogenesis, prognostic risk factors, therapy, outcome, and late effects of acute lymphocytic leukemia.