Abstract: Blocking the interaction of immune checkpoints and their ligands by immune checkpoint inhibitors (ICIs) may relieve immune cells from inhibition caused by immune checkpoints, thereby reinvigorating immune cells to exert anti-tumor effects. At present, numerous ICIs have witnessed remarkable progress in anti-tumor clinical application, which is a breakthrough in the field of tumor therapy. Inhibitors targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) have been successfully approved for the clinical treatment of various malignant tumors such as melanoma and non-small cell lung cancer. The great success of CTLA-4 and PD-1/PD-L1 antibody thus sets off a novel upsurge of research for ICIs. In recent years, more immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and cluster of differentiation 47 (CD47) have been identified. To this end, preclinical or clinical researches on these proteins have been extensively undertaken. This article reviews the extensively investigated immune checkpoints and their inhibitors, and introduces the molecular mechanisms of each immune checkpoint in tumor immunity as well as the progress of their inhibitors under clinical research.