Influenza viruses are significant human respiratory pathogens that cause seasonal and pandemic infections. The 1918 pandemic, the worst on record, killed about 50 million people. H5N1 avian influenza raises concerns about future pandemics. Histopathology of fatal influenza pneumonias shows similar changes across pandemics and seasonal outbreaks. The 1918 pandemic's pathology was not significantly different from other pandemics, but it had a higher fatality rate and an unusual age distribution. Influenza A viruses are the most important human influenza pathogens, with a variable histopathology. Autopsy studies focus on late-stage disease, and the spectrum of changes is similar across pandemics. H5N1 infections have limited data, but possible hypercytokinemia and extrapulmonary replication are noted. The 1918 pandemic virus had an avian-like genome and may have arisen through whole-genome adaptation. Influenza pathology includes tracheobronchial changes, epithelial damage, and alveolar inflammation. Histopathology of influenza pneumonia shows capillary thrombosis, alveolar damage, and hyaline membranes. Influenza virus pneumonia is characterized by severe complications, including secondary bacterial infections. Histopathologic changes in influenza include epithelial necrosis, desquamation, and inflammatory infiltrates. Influenza virus pneumonia in interpandemic cases shows similar features to pandemics. H5N1 infections in animals show extensive hemorrhage and alveolar damage. Experimental models show similar histopathologic features to humans, including hyaline membranes and capillary thrombosis. Nonhuman primates also show similar findings. Influenza virus infections in animals and humans share histopathologic features, but human cases show additional changes like hyaline membranes. Influenza virus infections in animals and humans share histopathologic features, but human cases show additional changes like hyaline membranes and capillary thrombosis.Influenza viruses are significant human respiratory pathogens that cause seasonal and pandemic infections. The 1918 pandemic, the worst on record, killed about 50 million people. H5N1 avian influenza raises concerns about future pandemics. Histopathology of fatal influenza pneumonias shows similar changes across pandemics and seasonal outbreaks. The 1918 pandemic's pathology was not significantly different from other pandemics, but it had a higher fatality rate and an unusual age distribution. Influenza A viruses are the most important human influenza pathogens, with a variable histopathology. Autopsy studies focus on late-stage disease, and the spectrum of changes is similar across pandemics. H5N1 infections have limited data, but possible hypercytokinemia and extrapulmonary replication are noted. The 1918 pandemic virus had an avian-like genome and may have arisen through whole-genome adaptation. Influenza pathology includes tracheobronchial changes, epithelial damage, and alveolar inflammation. Histopathology of influenza pneumonia shows capillary thrombosis, alveolar damage, and hyaline membranes. Influenza virus pneumonia is characterized by severe complications, including secondary bacterial infections. Histopathologic changes in influenza include epithelial necrosis, desquamation, and inflammatory infiltrates. Influenza virus pneumonia in interpandemic cases shows similar features to pandemics. H5N1 infections in animals show extensive hemorrhage and alveolar damage. Experimental models show similar histopathologic features to humans, including hyaline membranes and capillary thrombosis. Nonhuman primates also show similar findings. Influenza virus infections in animals and humans share histopathologic features, but human cases show additional changes like hyaline membranes. Influenza virus infections in animals and humans share histopathologic features, but human cases show additional changes like hyaline membranes and capillary thrombosis.