Immune containment of persistent viral infections has long been a focus of interest for investigators. However, the technologies needed to evaluate the role of CD8⁺ cytotoxic T lymphocytes (CTLs) in this process have only recently become available. Recent studies performed using tetramer, ELISPOT and cytokine-production assays have evaluated the role of CD8⁺ CTLs in controlling lentivirus and herpesvirus infections in humans and nonhuman primates. These studies demonstrate dramatic expansions of virus-specific CTLs in primary infection and the maintenance of unexpectedly high levels of virus-specific CTLs in chronic infection. These findings underscore the importance of CD8⁺ CTLs in the immune control of persistent viral infections.