Abstract: Immunotherapy is another breakthrough anti-tumor therapy, following traditional radiotherapy, chemotherapy, and targeted therapies. Immune checkpoint blockers (ICBs) have shown remarkable effects in the treatment of many malignant tumors. Given the prevalent application, ICB resistance is currently one of the most important issues in immunotherapy. This review discusses the possible mechanisms of ICB resistance, as well as methods for reversing ICB resistance, mainly through drug combinations, including combinations of radiation therapy, chemotherapy, targeted therapy, and other ICBs.