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In addition, there is growing evidence that DDX3 is a component of the innate immune response against viral infections. As such, DDX3 has been shown to play roles both upstream and downstream of I\u2010kappa beta kinase<jats:italic>\u03b5<\/jats:italic>(IKK<jats:italic>\u03b5<\/jats:italic>)\/TANK\u2010binding kinase 1, leading to IFN\u2010<jats:italic>\u03b2<\/jats:italic>production. Interestingly, several RNA viruses, including human threats such as HIV\u20101 and hepatitis C virus, hijack DDX3 to accomplish various steps of their replication cycles. Thus, it seems that viruses have evolved to exploit DDX3's functions while threatening the innate immune response. Understanding this interesting dichotomy in DDX3 function will help us not only to improve our knowledge of virus\u2013host interactions but also to develop novel antiviral drugs targeting the multifaceted roles of DDX3 in viral replication. 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