The specificity of antitumor immunity continues to attract interest as a potentially powerful mode of cancer treatment. Cancer vaccines and adoptive T-cell infusion are strategies that can increase the frequency of circulating tumor antigen-specific T-cells. However, although these approaches can produce clinical responses in a minority of patients, tumor escape from immune destruction appears to dominate in many instances. Several molecular mediators of tumor resistance to immune effector cells have been identified that can be targeted pharmacologically. Two of these, the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase and the T-cell inhibitory programmed death ligand 1, are discussed in this review. Blockade of these molecules may increase the efficacy of tumor-specific T-cell therapies in cancer patients.