Influenza viruses are major pathogens in humans and animals. Recent studies using gene-knockout mice have deepened understanding of innate sensors that detect influenza virus infection in various cell types. Signaling downstream of these sensors induces effector mechanisms that block virus replication and promote viral clearance by inducing innate and adaptive immune responses. This review discusses how the innate immune system uses pattern recognition receptors (PRRs) to detect and respond to influenza virus infection. It considers whether innate sensor stimulation promotes antiviral resistance or disease tolerance and proposes treatment strategies for acute respiratory disease caused by influenza virus. PRRs are host receptors that sense pathogen-associated molecular patterns and initiate signaling cascades leading to innate immune responses. Type I interferons (IFNs) are rapidly induced by virus infection and act on the IFN receptor to limit viral replication and enhance antigen-specific immune responses. Influenza virus is an enveloped virus with eight segments of negative-sense single-stranded RNA. It is recognized by antibodies and defines the virus subtype. Influenza viruses are classified as seasonal or pandemic based on genetic changes that dictate disease severity. The innate immune system provides a formidable barrier to influenza virus. Viral RNA in infected cells is recognized by PRRs, leading to secretion of type I IFNs, pro-inflammatory cytokines, eicosanoids, and chemokines. Type I IFNs stimulate the expression of IFN-stimulated genes (ISGs), inducing an antiviral state. Pro-inflammatory cytokines and eicosanoids cause inflammation, fever, and anorexia, and instruct adaptive immune responses. Chemokines recruit immune cells to the airways. Virally infected epithelial cells become targets of NK cells, which mediate viral clearance. Monocytes and neutrophils help clear infected dead cells. Phagocytic clearance of virus-infected cells by recruited phagocytes provides an important mechanism of viral clearance. If the virus establishes infection despite these defenses, adaptive immunity is required for clearance. Studies using mice deficient in innate sensors and signaling pathways have revealed their roles in innate resistance and host tolerance. Challenge with sublethal doses of influenza virus enables the host to survive by mounting a protective adaptive immune response. TLR3 recognizes dsRNA in endosomes, but due to the activity of the RNA helicase UAP56, it likely recognizes unidentified RNA structures in dying infected cells. TLR7 recognizes ssRNA in endosomes, leading to activation of NF-κB and IRF7, which stimulate pro-inflammatory cytokines and type I IFNs. TLR7 has a key role in innate defense in mice expressing MX1. TLR7 is important for eliciting robust antibody responses but not T cell responses. RIG-I detects replicating viral RNA in the cytosol of infected cells. RIG-I is crucial for viral detection and type I IFN production in infected epithelial cells, conventional DCs, and alveolarInfluenza viruses are major pathogens in humans and animals. Recent studies using gene-knockout mice have deepened understanding of innate sensors that detect influenza virus infection in various cell types. Signaling downstream of these sensors induces effector mechanisms that block virus replication and promote viral clearance by inducing innate and adaptive immune responses. This review discusses how the innate immune system uses pattern recognition receptors (PRRs) to detect and respond to influenza virus infection. It considers whether innate sensor stimulation promotes antiviral resistance or disease tolerance and proposes treatment strategies for acute respiratory disease caused by influenza virus. PRRs are host receptors that sense pathogen-associated molecular patterns and initiate signaling cascades leading to innate immune responses. Type I interferons (IFNs) are rapidly induced by virus infection and act on the IFN receptor to limit viral replication and enhance antigen-specific immune responses. Influenza virus is an enveloped virus with eight segments of negative-sense single-stranded RNA. It is recognized by antibodies and defines the virus subtype. Influenza viruses are classified as seasonal or pandemic based on genetic changes that dictate disease severity. The innate immune system provides a formidable barrier to influenza virus. Viral RNA in infected cells is recognized by PRRs, leading to secretion of type I IFNs, pro-inflammatory cytokines, eicosanoids, and chemokines. Type I IFNs stimulate the expression of IFN-stimulated genes (ISGs), inducing an antiviral state. Pro-inflammatory cytokines and eicosanoids cause inflammation, fever, and anorexia, and instruct adaptive immune responses. Chemokines recruit immune cells to the airways. Virally infected epithelial cells become targets of NK cells, which mediate viral clearance. Monocytes and neutrophils help clear infected dead cells. Phagocytic clearance of virus-infected cells by recruited phagocytes provides an important mechanism of viral clearance. If the virus establishes infection despite these defenses, adaptive immunity is required for clearance. Studies using mice deficient in innate sensors and signaling pathways have revealed their roles in innate resistance and host tolerance. Challenge with sublethal doses of influenza virus enables the host to survive by mounting a protective adaptive immune response. TLR3 recognizes dsRNA in endosomes, but due to the activity of the RNA helicase UAP56, it likely recognizes unidentified RNA structures in dying infected cells. TLR7 recognizes ssRNA in endosomes, leading to activation of NF-κB and IRF7, which stimulate pro-inflammatory cytokines and type I IFNs. TLR7 has a key role in innate defense in mice expressing MX1. TLR7 is important for eliciting robust antibody responses but not T cell responses. RIG-I detects replicating viral RNA in the cytosol of infected cells. RIG-I is crucial for viral detection and type I IFN production in infected epithelial cells, conventional DCs, and alveolar