Chemotherapy resistance in leukemia is an urgent clinical therapeutic challenge. Ferroptosis is a unique mode of cell death driven by iron-dependent phospholipid peroxidation. Leukemia is characterized by increased oxidative stress and iron overload, suggesting that leukemia cells might be susceptible to ferroptosis and indicating a possible therapeutic approach. Ferroptosis has been extensively studied in recent years and used in the treatment of various types of leukemia. Several studies have demonstrated an association between the regulatory pathways of ferroptosis and the mechanisms of leukemia drug resistance. The induction of ferroptosis through different pathways can effectively reduce the resistance of various types of leukemia cells to chemotherapeutic drugs, and thus improve their clinical efficacy. In this article, we review the regulatory mechanisms of ferroptosis and analyze the association between oxidative stress and iron metabolism pathways of ferroptosis and the mechanism of leukemia drug resistance. We also summarize the experimental studies and clinical applications of ferroptosis for the treatment of various types of drug-resistant leukemias, with the aim of providing new ideas and directions for the study of ferroptosis and a new strategy to reverse chemotherapy resistance in patients with leukemia in the future.