This chapter deals with interferons (IFNs), which were originally described as an activity found in the supernatant of virally infected cells that directly "interfered" with viral replication. These proteins are now known to represent a family of cytokines, and have been classified into two types based on structural and functional criteria, as well as the stimuli that elicit their expression. Type 1 IFNs are primarily induced in response to viral infection and have been divided into two groups: IFN-α, which is secreted largely by leukocytes, and IFN-β which is produced by fibroblasts. Type II IFN, now designated IFN-γ, is synthesized primarily by T lymphocytes and natural killer (NK) cells following activation with immune and inflammatory stimuli rather than viral infection. IFN-7 is currently one of the best understood members of the cytokine family. As the field moves further into the fine details of IFN-γ's functions and mechanisms of action, it is likely to gain new insights that will form a new foundation for the therapeutic use of this pleiotropic cytokine.