Despite extensive efforts, a preventive HIV vaccine has not yet been obtained and remains the main challenge in the field of AIDS research. Empirical approaches which have proved successful for many vaccines are not sufficient to tackle HIV-1 and new strategies to design effective preventive AIDS vaccines are critical. To this aim, further understanding of the mechanisms of action of neutralizing antibodies is required. In this review we summarize our current knowledge on the structure of the gp160 viral envelope and the dynamics of viral entry, the evolution of humoral response in HIV-infected patients and the mechanisms of viral escape. Finally, we describe the few neutralizing antibodies with activity against a broad spectrum of circulating HIV strains and their relevance in the design of new candidates to HIV-1 vaccines.