T lymphocytes require signaling by the T cell receptor and by nonclonotypic cosignaling receptors. The costimulatory and inhibitory signals profoundly influence the course of immune responses by amplifying or reducing the transcriptional effects of T cell receptor triggering. The inhibitory receptors such as CTLA-4, PD-1, and BTLA have recently drawn much attention as potential targets for immunotherapies. This review focuses on the progress that has been made with the mentioned receptors in the field of immunotherapies for autoimmune diseases, malignancies, infectious diseases, and transplantation.