A number of immune system components contribute to defense against viral infections. Although some of these overlap in part with those contributing to resistance against non-viral agents, the major anti-viral players comprise a unique subset. In particular, natural killer cells and CD8⁺ cytotoxic T cells are prominent in defense against viruses. With the exception of interferon-α/β, cytokine responses during viral infections have not been thoroughly characterized and are poorly understood with regard to in vivo expression and function. The availability of recombinant cytokines, assays to measure induced cytokine expression, and cytokine and cytokine receptor negative mice has made it possible to begin to characterize other factors contributing to defense and immune regulation during viral infections. Advances have been made in characterizing the expression and functions of interferon-γ, IL-2, IL-4, IL-10, transforming growth factor-β, and IL-12. The results thus far suggest that there are at least three different stages of immune responses to viral infections and that unique cytokine profiles are associated with each of these stages.