In this study, we show that IFN-αβ can have a direct role in linking innate and adaptive responses by providing the “third signal” needed by naive CD8 T cells responding to Ag and costimulatory ligands. Stimulation of CD8 T cells in the absence of a third signal leads to proliferation, but clonal expansion is limited by poor survival and effector functions do not develop. We show that IFN-αβ can provide the third signal directly to CD8 T cells via a STAT4-dependent pathway to stimulate survival, development of cytolytic function, and production of IFN-γ. Provision of the third signal by either IFN-αβ or IL-12 results in regulation of the expression of a number of genes, including several that encode proteins critical for effector function.