Programmed cell death protein 1 (PD-1 or CD279) is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T cells, B cells, monocytes, and dendritic cells. PD-1 plays an important role as an immune checkpoint. PD-1 binds to two ligands, PD-L1 and PD-L2. The PD-1/PD-L1 or PD-L2 signaling pathway is a negative regulatory mechanism that inhibits T cell proliferation and cytokine production. PD-1 inhibitors play a role in activation of the immune system and can be used for cancer treatment. Blockade of the PD-1/PD-L1 interaction enhances anti-tumor immunity and shows potential for improving cancer immunotherapy. The PD-1 pathway plays a major role in the inhibition of self-reactive T cells and protection against autoimmune diseases.