Interferons (IFNs) comprise a family of secreted α-helical cytokines induced in response to specific extracellular biomolecules through stimulation of Toll-like receptors (TLRs). Acting in paracrine or autocrine modes, IFNs stimulate intra- and intercellular networks for regulating innate and acquired immunity, resistance to viral infections, and normal and tumor cell survival and death (Table 53-1 ). Through high-affinity cell surface receptors, IFNs stimulate genes, employing signaling molecules also used in part by other cytokines first identified through studies of IFNs. Perturbations in these pathways can also make cells resistant to a given ligand, facilitating either progression or resistance of malignancy. IFNs act on almost every cell type and, through their cellular actions, can be effective in inhibiting tumor emergence and progression and in inducing regression (see Table 53-1).