Acute lymphoblastic leukemia (ALL) is a malignant hematologic tumor with highly aggressive characteristics, which has few clinically effective drugs. It is meaningful to gain a better understanding of its pathogenesis in order to discover and evaluate potential therapeutic drugs and new treatment targets. However, the process of new drugs from research and development to clinical application is long and difficult. Many promising drugs were rejected by the US Food and Drug Administration (FDA) due to serious adverse drug reactions (ADR) in clinical phase I trials. Animal models provide us with an excellent tool to understand the complex pathological mechanisms of human diseases, to evaluate the potential of new targeted drugs and to assess the potential ADR they may have on healthy organs. In this article we briefly introduce the clinical status of ALL, review ALL animal models’ progression, their roles in revealing the pathogenesis of ALL and drug development.