Influenza virus is one of global constant research highlights, because it can cause the most severe disease in humans and animals as well as the most likely to trigger a pandemic. The surface glycoprotein hemagglutinin (HA) is critical determinants of the host specificity, virulence and infectivity of the influenza virus. The genetic mutations and glycosylation of HA can affect the biological properties of HA. The binding of HA to sialylated glycan receptors on host epithelial cells is the critical initial step in the infection and transmission of the virus. Understanding these components is important in comprehending the infection and the transmission of both existing human influenza viruses and newly emerging avian influenza viruses. This review summarizes studies how influenza virus and receptor components might act as determinants for successful viral replication and transmission and new progress for understanding the role of the structure of sialylated glycan receptors in influenza virus pathogenesis.