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Many studies have been conducted over the last few decades to understand better the functions of IRF3 and IRF7 in antiviral immune responses. However, the precise underlying molecular mechanism of IRF1-mediated immune response remains largely unknown. Recent studies indicate that IRF1 exerts strong antiviral activities against several viral infections through diverse mechanisms, both in IFN-dependent and IFN-independent manners. Nevertheless, the efficacy and kinetics of inducing IFNs and ISGs remain unknown. Here we summarize the recent advances in IRF1 research and highlight its potential roles in initiating IFN immune responses and subsequent IRF1-triggering antiviral responses. Challenges regarding the IFN positive feedback mediated by IRF7 during infection will be discussed; this classical loop may also be mediated in part by IRF1. Therefore, we propose a revised model that may help decipher the functional roles of IRF1 in antiviral immunity. [Display omitted] • IRF1 induces both IFN production and basal level of ISGs. • IRF1 involves an interferon induction in an IRF3 and IRF7 independent manner. • IRF1 is involved in the modification of JAK1, STAT1. • IRF1 is involved in the epigenetic regulation of ISGs. • Viruses evolve to antagonize the IRF1 mediated signaling pathway. [ABSTRACT FROM AUTHOR]