The article by John W. Schoggins and Charles M. Rice discusses the role of interferon-stimulated genes (ISGs) in antiviral defense. ISGs are transcriptionally induced by type I interferons (IFNs) and play a crucial role in mounting an immune response against viral infections. The authors highlight recent efforts to identify new antiviral ISGs and review emerging themes in their effector functions and mechanisms of action. They emphasize that ISGs can target various steps in the viral life cycle, including early post-entry events, and that their antiviral activity varies widely. The article also explores the combinatorial antiviral properties of ISGs, where the combined expression of multiple ISGs can enhance the antiviral response. Additionally, the authors discuss the complex interactions between ISGs and viral countermeasures, such as viral evasion mechanisms that counteract ISG-induced antiviral activities. The study underscores the importance of ISGs in antiviral defense and their potential as therapeutic targets for treating viral infections.The article by John W. Schoggins and Charles M. Rice discusses the role of interferon-stimulated genes (ISGs) in antiviral defense. ISGs are transcriptionally induced by type I interferons (IFNs) and play a crucial role in mounting an immune response against viral infections. The authors highlight recent efforts to identify new antiviral ISGs and review emerging themes in their effector functions and mechanisms of action. They emphasize that ISGs can target various steps in the viral life cycle, including early post-entry events, and that their antiviral activity varies widely. The article also explores the combinatorial antiviral properties of ISGs, where the combined expression of multiple ISGs can enhance the antiviral response. Additionally, the authors discuss the complex interactions between ISGs and viral countermeasures, such as viral evasion mechanisms that counteract ISG-induced antiviral activities. The study underscores the importance of ISGs in antiviral defense and their potential as therapeutic targets for treating viral infections.