Swine-origin H1N1 influenza virus (S-OIV) emerged in 2009 and caused a global pandemic. It is a reassortant of avian, human, and swine influenza viruses, with genes from North American avian and classical swine viruses, and Eurasian avian-like swine viruses. S-OIVs spread efficiently among humans but caused relatively few fatalities, unlike the 1918 Spanish influenza, which had high mortality rates. The 1918 virus was avian-like but had a unique HA cleavage site that allowed efficient replication in humans. S-OIVs have a human-like HA receptor binding site, which supports efficient transmission. The HA protein is critical for viral entry and fusion, and its amino acid sequence determines receptor specificity. S-OIVs have a 'human virus'-type amino acid at positions 190 and 225, which supports efficient transmissibility. The PB2 protein also plays a role in pathogenicity, with lysine at position 627 allowing efficient replication in the upper respiratory tract. The NS1 protein is an interferon antagonist that blocks the activation of transcription factors and IFN-β-stimulated genes. The PB1-F2 protein induces apoptosis and enhances inflammation. The S-OIVs are sensitive to neuraminidase inhibitors. Antiviral drugs such as oseltamivir and zanamivir are effective against influenza viruses, but resistance is a concern. Vaccines are available for seasonal influenza, but new vaccines are needed for emerging strains. Live attenuated vaccines are effective but require careful handling. The emergence of S-OIVs highlights the need for continued surveillance and research to understand the factors that determine viral pathogenicity and transmissibility. The development of improved vaccines and antiviral drugs is critical for controlling influenza outbreaks.Swine-origin H1N1 influenza virus (S-OIV) emerged in 2009 and caused a global pandemic. It is a reassortant of avian, human, and swine influenza viruses, with genes from North American avian and classical swine viruses, and Eurasian avian-like swine viruses. S-OIVs spread efficiently among humans but caused relatively few fatalities, unlike the 1918 Spanish influenza, which had high mortality rates. The 1918 virus was avian-like but had a unique HA cleavage site that allowed efficient replication in humans. S-OIVs have a human-like HA receptor binding site, which supports efficient transmission. The HA protein is critical for viral entry and fusion, and its amino acid sequence determines receptor specificity. S-OIVs have a 'human virus'-type amino acid at positions 190 and 225, which supports efficient transmissibility. The PB2 protein also plays a role in pathogenicity, with lysine at position 627 allowing efficient replication in the upper respiratory tract. The NS1 protein is an interferon antagonist that blocks the activation of transcription factors and IFN-β-stimulated genes. The PB1-F2 protein induces apoptosis and enhances inflammation. The S-OIVs are sensitive to neuraminidase inhibitors. Antiviral drugs such as oseltamivir and zanamivir are effective against influenza viruses, but resistance is a concern. Vaccines are available for seasonal influenza, but new vaccines are needed for emerging strains. Live attenuated vaccines are effective but require careful handling. The emergence of S-OIVs highlights the need for continued surveillance and research to understand the factors that determine viral pathogenicity and transmissibility. The development of improved vaccines and antiviral drugs is critical for controlling influenza outbreaks.