Acute lymphoblastic leukemia (ALL), the most common type of cancer in children, is a heterogeneous disease in which many genetic lesions result in the development of multiple biologic subtypes. Today, with intensive multiagent chemotherapy, most children who have ALL are cured. The many national or institutional ALL therapy protocols in use tend to stratify patients in a multitude of different ways to tailor treatment to the rate of relapse. This article discusses the factors used in risk stratification and the treatment of pediatric ALL.