In this article the mode of infection with HIV-1 virus and the role of glycoprotein 120 (gp120) in this process were described. The gp120 is responsible for a number of phenomena resulting from HIV-1 infection. Against the epitopes of gp120 humoral and cellular responses develop. However, because of a high variability of this protein, caused by mutations, in the process of infection these responses become ineffective. Moreover, gp120, as revealed from numerous studies, causes a decrease in the number of peripheral blood CD4+ T lymphocytes, both infected and uninfected. This is caused by induction and participation in the processes such as: inhibition of CD4 receptor expression on the surface of infected lymphocyte, formation of syncytia, antibody-dependent cell-mediated cytotoxicity and apoptosis. Together with other factors, these processes result in developing of fully symptomatic acquired immunodeficiency syndrome (AIDS).