The elaboration of a successful immune response is critical for the clearance of viral infections. CD8 T cells can directly kill virus-infected cells and also produce cytokines that modulate virus replication. Thus, the failure to induce or sustain these responses can profoundly impact the outcome of infections. Lymphocytic choriomeningitis virus (LCMV) infection of mice has proven to be one of the most informative experimental systems for examining antiviral T cell responses. In recent years, the application of newly developed approaches to analyze these responses has revealed that acute infections induce remarkably high levels of antiviral T cells. By contrast, protracted or chronic infections are associated with both the functional impairment and deletion of virus-specific CD8 T cells. This article discusses some of our findings using LCMV infection of mice as well as their relevance to other infections of animals and humans.