Management of an immune response is achieved through a delicate balance of pro-inflammatory and anti-inflammatory mechanisms. Controlling this response requires co-operation between a multitude of immune cells that are in turn controlled by specific receptor-ligand interactions and cytokine networks. In the context of cancer, a major mechanism by which the immune system restrains disease is through the action of cytotoxic lymphocytes that include natural killer (NK) cells and CD8 T cells. Both of these cell types express a panoply of receptors that are able to control their responses in order to heighten the specificity of their effector function. An emerging class of such receptors on cytotoxic lymphocytes are a group of immunoglobulin superfamily members that interact with ligands of the nectin and nectin-like (necl) family. These receptors include CD226, TIGIT, CRTAM and CD96. This review will outline the immunobiology of these receptors, the contexts where their function is important, their role in tumour immunosurveillance, and how they may be utilised for therapeutic applications in cancer.