Lymphohematopoietic neoplasias represent a heterogeneous group of clonal hematopoietic and lymphoid cell disorders and are one of the most common types of cancer induced by environmental and therapeutic agents. Leukemia is a lymphohematopoietic cancer originating in the bone marrow that affects cells of either the myeloid lineages (myeloid leukemia) or the lymphoid lineage (lymphoid or lymphoblastic leukemia). These can be further categorized as acute or chronic depending upon the rate of clonal expansion or stage of differentiation of the cancer cell. The objective of this report is to provide an overview of the types and mechanisms underlying the lymphohematopoietic cancers induced by chemical agents and radiation in humans, with a primary emphasis on AML and agents that induce this type of cancer. Following a brief discussion of hematopoiesis and leukemogenesis, a review of the major classes of leukemia-inducing agentsradiation, chemotherapeutic alkylating agents, and topoisomerase II inhibitorsis presented along with information on the mechanisms by which these leukemias occur. The last section focuses on how mechanistic information on human leukemia-inducing agents can be used to better inform risk assessment decisions.