Interferons (IFNs) elicit multifaceted effects in host innate defence. Accumulating evidence revealed that not only the first identified Jak‐Stat pathway but also other newly found signalling pathways are required for the induction of versatile responses by IFNs. In particular, type I IFNs are inducible by viral infection through the recognition of pathogen‐associated molecules by pattern recognition receptors, and the induction of multiple IFN‐stimulated genes through the activation of type I IFN signalling confers antiviral and immunomodulatory activities. Any step in this process is often targeted by viruses for their immuno‐evasion. The regulatory function of constitutive IFN‐α/β signalling has been recognized in terms of its boosting effect on cellular responsiveness in host defence systems. Further comprehensive understanding of IFN signalling may offer a better direction to unravelling the complex signalling networks in the host defence system, and may contribute to their more effective therapeutic applications.