Host responses to infectious challenges include initial events elicited directly by agent structures distinct from host determinants, activation of innate immune system components by the products of initial events, and the shaping of downstream adaptive immunity by these initial/innate responses. The picture emerging from viral infections is that viral structures interact with intracellular signaling pathways to induce expression of the type 1 interferons, IFN-α/β. In addition to mediating direct antiviral effects, these cytokines play dominant roles in regulating innate and adaptive immune responses to infection. In particular, IFN-α/β acts to inhibit interleukin-12 (IL-12) expression and IL-12 activation of innate natural killer (NK) cell IFN-γ production, while inducing NK cell cytotoxicity and proliferation, and promoting adaptive T cell IFN-γ responses. Although certain viral infections do elicit initial/innate IL-12 and NK-cell-produced IFN-γ, endogenous IFN-α/β also controls the magnitudes of these responses. Thus, the pathways activated, to dominantly regulate innate and adaptive immune responses during viral infections, are being defined.