NKG2D is a potent activating receptor on NK cells and a co-stimulatory receptor on CD8+ T cells. Through its ability to recognize a panel of ligands inducible by stress or infection, it plays an important role in the control of viral infections. The viruses have evolved robust mechanisms to counteract NKG2D-dependent immune response. The functions of these viral inhibitors are well characterized during the early days post-infection but less so during the chronic viral infection.