Influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus (IAV). Some human-adapted strains of H1N1 are endemic in humans and are one cause of seasonal influenza (flu). Other strains of H1N1 are endemic in pigs (swine influenza) and in birds (avian influenza). Subtypes of IAV are defined by the combination of the antigenic hemagglutinin (H) and neuraminidase (N) proteins in the viral envelope; for example, "H1N1" designates an IAV subtype that has a type-1 H protein and a type-1 N protein.

All subtypes of IAV share a negative-sense, segmented RNA genome. Under rare circumstances, one strain of the virus can acquire genetic material through genetic reassortment from a different strain and thus evolve to acquire new characteristics, enabling it to evade host immunity and occasionally to jump from one species of host to another. Major outbreaks of H1N1 strains in humans include the 1918 Spanish flu pandemic, the 1977 Russian flu pandemic and the 2009 swine flu pandemic, all of which were caused by strains of A(H1N1) virus which are believed to have undergone genetic reassortment.

Each year, three influenza strains are chosen for inclusion in the forthcoming year's seasonal flu vaccination by the Global Influenza Surveillance and Response System of the World Health Organization (WHO). Since 1999, every annual formulation has included one strain of A/H1N1 as well as two other influenza strains – together representing strains thought most likely to cause significant human suffering in the coming season.

Swine influenza (also known as swine flu or pig flu) is a respiratory disease that occurs in pigs that is caused by the Influenza A virus. Influenza viruses that are normally found in swine are known as swine influenza viruses (SIVs). The three main subtypes of SIV that circulate globally are A(H1N1), A(H1N2), and A(H3N2). These subtypes are well adapted to pigs and are different from human influenza viruses of the same subtype.

Swine influenza virus is common throughout pig populations worldwide. Transmission of the virus from pigs to humans is not common and does not always lead to human influenza, often resulting only in the production of antibodies in the blood. If transmission does cause human influenza, it is called zoonotic swine flu or a variant virus. People with regular exposure to pigs are at increased risk of swine flu infection. Properly cooking the meat of an infected animal removes the risk of infection.

Pigs experimentally infected with the strain of swine flu that caused the human pandemic of 2009–10 showed clinical signs of flu within four days, and the virus spread to other uninfected pigs housed with the infected ones.

The 1918 flu was an unusually severe and deadly strain of H1N1 swine influenza, which killed from 17 to 50 or more million people worldwide over about a year in 1918 and 1920. It was one of the deadliest pandemics in human history.

The 1918 flu caused an abnormally high number of deaths, possibly due to it provoking a cytokine storm in the body. (The H5N1 bird flu, also an Influenza A virus, has a similar effect.) After the 1918 flu infected lung cells, it frequently led to overstimulation of the immune system via release of immune response-stimulating cytokines (proteins that transmit signals between cells) into the lung tissue. This leads to extensive leukocyte migration towards the lungs, resulting in the destruction of lung cells and secretion of blood and mucus into the alveoli and airways. This makes it difficult for the patient to breathe and can result in suffocation. In contrast to other pandemics, which mostly kill the old and the very young, the 1918 pandemic killed unusual numbers of young adults, which may have been due to their healthy immune systems mounting a too-strong and damaging response to the infection.