Influenza viruses infect the upper respiratory system, causing usually a self-limited disease with mild respiratory symptoms. Acute lung injury, pulmonary microvascular leakage and cardiovascular collapse may occur in severe cases, usually in the elderly or in immunocompromised patients. Acute lung injury is a syndrome associated with pulmonary edema, hypoxemia, and respiratory failure. Influenza virus primarily binds to the epithelium, interfering with the epithelial sodium channel (EnaC) function. However, the main clinical devastating effects are casued by endothelial dysfunction, thought to be the main mechanism leading to pulmonary edema, respiratory failure and cardiovascular collapse.A significant association was found between influenza infection and acute myocardial infarction (AMI). The incidence of admission due to AMI during an acute viral infection was 6 times as high during the 7 days after laboratory confirmation of influenza infection as during the control interval (10 fold in influenza B, 5 fold in influenza A, 3.5 fold in respiratory syncytial virus, and 2.7 fold for all other viruses).Our review will focus on the mechanisms responsible for endothelial dysfunction during influenza infection leading to cardiovascular collapse and death.