Colorectal cancer (CRC), as a prominent cause of cancer-related deaths, has historically been notable worldwide and many attempts have been made to raise the overall survival of CRC patients. Immune response has long been a question of great interest in a wide range of fields such as cancer therapies and anti-tumor immunity through checkpoint inhibitors, specifically anti PD-1/ PD-L1 interaction, is a new line of research for treatment of CRC patients. Following the successful development of anti-PD-1 for melanoma, renal cell carcinoma, and non-small cell lung cancer, several clinical trials have been conducted on monoclonal antibodies (MAbs) against PD-1 in CRC. There is a growing body of literature that recognizes the importance of anti-PD-1 therapy for MSI (Microsatellite instability) tumors among CRC subtypes. We present a comprehensive knowledge of immune therapy through PD-1/PD-L1 blockade that argues how efficient the process is, in colon cancer carcinoma. In this review, we discuss the responsiveness of immunotherapy on PD-1/PD-L1 blockade and various tactics for overcoming weak responses to these checkpoint inhibitors in CRC. More research using controlled trials is required to enable new discoveries to provide continued success with immune-based therapies and grounds for optimism about the future of CRC patients.