A major turning point for tumor immunotherapy was the discovery of immune checkpoint proteins, which suppress immunity to facilitate tumor growth. The discovery prompted the development of immune checkpoint inhibitors (ICIs) that can help fight even metastatic and chemoresistant cancers. ICIs that target the proteins CTLA-4, PD-1, and PD-L1 are particularly promising for cancer treatment. These drugs can be used either alone or with other therapies to enhance treatment efficacy. For example, they can be combined with traditional chemotherapy, radiotherapy, antiangiogenic therapy, and cancer vaccines to improve outcomes. In addition, combinations of CTLA-4- and PD-1-blocking ICIs can be used to treat cancers like melanoma. However, despite the encouraging results in some studies, many patients fail to respond to ICIs. ICIs can also exert various immune-related adverse effects on the skin, colon, liver, lungs, kidneys, and heart, and some tumors can become resistant to the drugs. Given these drawbacks, more work is needed to optimize the use of ICIs in order to maximize their efficacy against tumor cells while reducing their toxicity to normal cells.