Immune checkpoint inhibitors (ICIs) mainly include pembrolizumab, nivolumab and ipilimumab, which have changed the standard treatment for many types of cancer. In colorectal cancer (CRC), the status of microsatellite instability (MSI) or mismatch repair (MMR) is the most important factor affecting the efficacy of ICIs. Metastatic CRC (mCRC) with microsatellite instability-high (MSI-H) or MMR deficiency (dMMR) usually has a tumor microenvironment T-cell infiltration and is associated with a good response to ICIs, but the proportion of mSI-H/dMMR accounts for less than 5% of the mCRC. Paprizumab and navumab with or without combination of ipilimumab have been included in the standard treatment regimen for MSI-H/dMMR mCRC. In contrast, low T-cell infiltration in tumor microenvironments of mCRCs with microsatellite stable (MSS) or mismatch repair stable (pMMR) is considered to be the main mechanism of ICIs resistance. Here, the authors review the existing clinical data and some ongoing clinical trials of ICIs for CRC treatment, and discuss the possible limitations.