Hemagglutinin (HA) and neuraminidase (NA) are major glycoproteins expressed on the surface of influenza virus. They have complementary and antagonistic functions that facilitate in the life cycle of the virus. The functional equilibrium generated between HA and NA can impact the evolution and adaptation of influenza virus strains within the human reservoir. This functional equilibrium is referred to as the "HA-NA balance". An imbalanced HA-NA can restrict the multiplication and transmission capacity of influenza viruses. Moreover, this equilibrium is likely a limiting factor against species crossover for the virus. In light of such considerations, the HA-NA balance should be precisely studied to gain a better understanding of the emergence of pandemic and seasonal influenza virus strains. This review describes the concept of the HA-NA balance, the methods used to study it, plus a discussion of the HA-NA balance in the evolution of the pandemic influenza A H1N1 strains that plagued the world in 1918 and 2009.