Three years ago, two research groups independently identified a previously undescribed T cell cosignaling molecule; one referred to it as V-domain Ig suppressor of T cell activation (VISTA), and the other used the term programmed death-1 homolog (PD-1H). Recombinant and ectopically expressed PD-1H functions as a coinhibitory ligand for T cell responses. However, the function of endogenous PD-1H is not clear. In this issue of the JCI, Flies and colleagues demonstrate that endogenous PD-1H on both T cells and APCs serves as a coinhibitory molecule for T cell activation and provide further support for targeting PD-1H as a therapeutic strategy for transplantation and cancers.