Despite seasonal vaccines, influenza‐related hospitalization and death rates have remained unchanged over the past 5 years. Influenza pathogenesis has 2 crucial clinical components; first, influenza causes acute lung injury that may require hospitalization. Second, acute injury promotes secondary bacterial pneumonia, a leading cause of hospitalization and disease burden in the United States and globally. Therefore, developing an effective therapeutic regimen against influenza requires a comprehensive understanding of the damage‐associated immune‐mechanisms to identify therapeutic targets for interventions to mitigate inflammation/tissue‐damage, improve antiviral immunity, and prevent influenza‐associated secondary bacterial diseases. In this review, the pathogenic immune mechanisms implicated in acute lung injury and the possibility of using lung inflammation and barrier crosstalk for developing therapeutics against influenza are highlighted.

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