The article provides a comprehensive overview of the past, current, and future impact of interferons (IFNs) on biomedicine. IFNs, discovered in 1957, have evolved from being recognized as antiviral agents to being pivotal in oncology and multiple sclerosis (MS) treatment. The discovery and molecular understanding of IFNs have significantly advanced biomedicine over the past 50 years. IFNs are secreted autocrine and paracrine proteins that regulate resistance to viral infections, enhance innate and acquired immune responses, and modulate normal and tumor cell survival and death. The induction of IFNs is mediated through Toll-like receptors (TLRs), and their actions are mediated through signaling pathways involving Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. The article highlights the importance of IFN-stimulated genes (ISGs) in mediating the biological and therapeutic effects of IFN stimulation. ISGs include proteins that inhibit viral replication, promote apoptosis, and modulate immune responses. The clinical applications of IFNs have expanded to include the treatment of chronic viral infections, such as hepatitis B and C, and the management of MS. The article also discusses the potential for developing new drugs that target different components of the IFN system for various therapeutic indications. Finally, it outlines important research questions for the future, including the identification of novel ISGs and the development of more effective and less expensive treatments.The article provides a comprehensive overview of the past, current, and future impact of interferons (IFNs) on biomedicine. IFNs, discovered in 1957, have evolved from being recognized as antiviral agents to being pivotal in oncology and multiple sclerosis (MS) treatment. The discovery and molecular understanding of IFNs have significantly advanced biomedicine over the past 50 years. IFNs are secreted autocrine and paracrine proteins that regulate resistance to viral infections, enhance innate and acquired immune responses, and modulate normal and tumor cell survival and death. The induction of IFNs is mediated through Toll-like receptors (TLRs), and their actions are mediated through signaling pathways involving Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins. The article highlights the importance of IFN-stimulated genes (ISGs) in mediating the biological and therapeutic effects of IFN stimulation. ISGs include proteins that inhibit viral replication, promote apoptosis, and modulate immune responses. The clinical applications of IFNs have expanded to include the treatment of chronic viral infections, such as hepatitis B and C, and the management of MS. The article also discusses the potential for developing new drugs that target different components of the IFN system for various therapeutic indications. Finally, it outlines important research questions for the future, including the identification of novel ISGs and the development of more effective and less expensive treatments.