Acute lymphoblastic leukemia is the most common malignancy in children. Inspite of the tremendous progress in diagnosis and treatment little is known about leukemogenesis. Many causes have been implicated in etiology. Recently, there has been great interest in gene-environment interaction as a risk modifier of acute lymphoblastic leukemia. Mutations in genes coding for enzymes involved in activation or detoxification of carcinogens affect the activity of these enzymes leading to decreased or increased risk of acute lymphoblastic leukemia. The impact of these mutations differs according to ethnic groups and environmental exposure.