The threat of a new influenza pandemic is real . With past pandemics claiming millions of lives, finding new ways to combat this virus is essential . Host cells have developed a multi-modular system to detect incoming pathogens, a phenomenon called sensing . The signaling cascade triggered by sensing subsequently induces protection for themselves and their surrounding neighbors, termed interferon (IFN) response . This response induces the upregulation of hundreds of interferon-stimulated genes (ISGs), including antiviral effectors, establishing an antiviral state . As well as the antiviral proteins induced through the IFN system, cells also possess a so-called intrinsic immunity, constituted of antiviral proteins that are constitutively expressed, creating a first barrier preceding the induction of the interferon system . All these combined antiviral effectors inhibit the virus at various stages of the viral lifecycle, using a wide array of mechanisms . Here, we provide a review of mammalian and avian influenza A restriction factors, detailing their mechanism of action and in vivo relevance, when known . Understanding their mode of action might help pave the way for the development of new influenza treatments, which are absolutely required if we want to be prepared to face a new pandemic.