Leukemia is a hematological malignancy associated with the uncontrolled proliferation of mutant progenitors, suppressing the production of normal blood cells. Current treatments, including chemotherapy, radiotherapy, and immunotherapy, still lead to unsatisfactory results with a 5 year survival rate of only 30-50%. The poor prognosis is related to both disease relapse and treatment-associated toxicity. Delivery strategies can improve the in vivo pharmacokinetics of drugs, navigating the therapeutics to target cells or the tumor microenvironment and reversing drug resistance, which maximizes tumor elimination and alleviates systematic adverse effects. This review discusses available FDA-approved anti-leukemia drugs and therapies with a focus on the advances in the development of anti-leukemia drug delivery systems. Additionally, challenges in clinical translation of the delivery strategies and future research opportunities in leukemia treatment are also included.