Based on T cell subset depletion studies and the analysis of gene knockout mice, it is evident that CD8⁺ T cells contribute to resistance against intracellular infections with certain viral, protozoan, and bacterial pathogens. Although they are known primarily for their capacity to kill infected cells, CD8⁺ T cells elaborate a variety of effector mechanisms with the potential to defend against infection. Microbes use multiple strategies to cause infection, and the nature of the pathogenhost interaction may determine which CD8⁺ T cell effector mechanisms are required for immunity. In this review, we summarize our current understanding of the effector functions used by CD8⁺ T cells in resistance to pathogens. Analyses of mice deficient in perforin and/or Fas demonstrate that cytolysis is critical for immunity against some, but not all, infections and also reveal the contribution of cytolysis to the pathogenesis of disease. The role of CD8⁺ T cell–derived cytokines in resistance to infection has been analyzed by systemic treatment with neutralizing antibodies and cytokine gene knockout mice. These studies are complicated by the fact that few, if any, cytokines are uniquely produced by CD8⁺ T cells. Thus, the requirement for CD8⁺ T cell– derived cytokines in resistance against most pathogens remains to be defined. Finally, recent studies of human CD8⁺ T cells reveal the potential for novel effector mechanisms in resistance to infection.