Abstract: NKG2D, an activating immunoreceptor, plays a critical role in tumor immunity, infection immunity and autoimmune diseases. Engagement of NKG2D ligands on tumor cells by NKG2D triggers effector cells to eliminate tumor cells. This leads to the hypothesis that NKG2D-mediated cytolytic function would be one of the mechanisms of tumor immune surveillance. Recently intensive researches have shown that NKG2D ligands expressed on leukemia cells are involved in leukemia immune surveillance. This review summarizes some of recent discoveries about the roles of NKG2D and its ligands in immune surveillance and immune evasion of leukemia.