Interferon-stimulated genes (ISGs) play a critical role in the host's defense against pathogens. This review discusses the functions of ISGs, their role in innate immunity, and their impact on viral and bacterial infections. ISGs are involved in enhancing pathogen sensing, regulating the JAK-STAT signaling pathway, and directly inhibiting viral infection. The review also highlights the importance of maintaining strict control over IFN signaling to prevent autoimmune disorders. ISGs are categorized into different types, including type I, type II, and type III IFNs, each with distinct functions and signaling pathways. The JAK-STAT pathway is central to ISG regulation, and its activation leads to the transcription of numerous ISGs that contribute to the antiviral state. ISGs can also desensitize cells to IFN signaling, allowing them to recover from the IFN-induced state. The review also discusses the antiviral mechanisms of various ISGs, including their roles in inhibiting virus entry, translation, and egress. Overall, ISGs are essential for the host's defense against pathogens and are a key component of the innate immune response.Interferon-stimulated genes (ISGs) play a critical role in the host's defense against pathogens. This review discusses the functions of ISGs, their role in innate immunity, and their impact on viral and bacterial infections. ISGs are involved in enhancing pathogen sensing, regulating the JAK-STAT signaling pathway, and directly inhibiting viral infection. The review also highlights the importance of maintaining strict control over IFN signaling to prevent autoimmune disorders. ISGs are categorized into different types, including type I, type II, and type III IFNs, each with distinct functions and signaling pathways. The JAK-STAT pathway is central to ISG regulation, and its activation leads to the transcription of numerous ISGs that contribute to the antiviral state. ISGs can also desensitize cells to IFN signaling, allowing them to recover from the IFN-induced state. The review also discusses the antiviral mechanisms of various ISGs, including their roles in inhibiting virus entry, translation, and egress. Overall, ISGs are essential for the host's defense against pathogens and are a key component of the innate immune response.