Extract: Annual influenza (flu) epidemics in humans affect 5-15% of the population, causing an estimated half million deaths worldwide per year. Antibodies against the viral surface glycoprotein hemagglutinin (HA) provide protective immunity to influenza virus infection and this protein is therefore the primary component of influenza vaccines. However, the antigenic structure of HA has changed significantly over time, a process known as antigenic drift. In as many years, antigenic drift necessitates an update of the influenza vaccine to ensure sufficient efficacy against newly emerging virus variants. Antigenic drift is therefore both the root cause of the enormous public health burden of influenza epidemics, and a primary reason why the virus is such a fascinating pathogen from a scientific perspective. Thousands of influenza viruses are isolated and analyzed each year by the national and international laboratories that form the World Health Organization (WHO) global influenza surveillance network. This worldwide surveillance effort produces the data for the twice-yearly vaccine strain selection meetings, and has resulted in the establishment of a remarkable historical record of the global evolution of this important pathogen. The degree to which immunity induced by one strain is effective against another is mostly dependent on the extent of the antigenic difference between the strains. The analysis of antigenic differences between strains is therefore critical for surveillance and vaccine strain selection, and is also a cornerstone of basic and applied research in virology.