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Abstract Background Immune checkpoint proteins, especially PD-L1 and PD-1, play a crucial role in controlling the intensity and duration of the immune response, thus preventing the development of autoimmunity. These proteins play a vital role in enabling cancer cells to escape immunity, proliferate and progress. Methods This brief review highlights essential points related to testing for immune checkpoint therapy that histopathologists need to know. Results In recent years, several inhibitors of these proteins have been used to reactivate the immune system to fight cancer. Selection of patients for such therapy requires demonstration of PD-L1 activation on the tumor cells, best done by immunohistochemical staining of the tumor and immune cells using various antibodies with predetermined thresholds. Conclusions Immune checkpoint therapy appears to be promising and is rapidly expanding to include a large variety of cancers.