Leukemia is a life threatening disease that has become increasingly common. Many categories of anti-leukemic agents have been developed by probing into the nature of leukemia. Nevertheless, the needs for potent molecules with few side effects are still not satisfied in the current anti-leukemic therapy. Targeted therapy has been developed for the advantage of relatively high efficiency and safety in the anticancer chemotherapy. Among the targeted antitumor therapies, inhibition of histone deacetylases has been intensively studied. Three histone deacetylase inhibitors (HDACIs) have been approved by US Food and Drug administration (FDA) for the treatment of cancer. Interestingly, a number of HDACIs selectively exhibited inhibitory effects on leukemic cell lines in the preclinical researches. Herein, the anti-leukemic HDACIs were reviewed to gain insight into HDACIs' potential as anti-leukemic agents.