Individuals infected with HIV-1 and nearly everyone vaccinated with HIV-1 vaccines will, in time, generate antibodies against viral proteins. These antibodies do not resolve natural infection, and vaccine candidates that successfully stimulate the production of high titers of neutralizing antibodies have failed to protect against infection. In spite of this, antibodies continue to be a focus of vaccine research. One reason for the continued interest in antibodies is the failure of a vaccine engineered to generate cell-mediated immunity against HIV. Successful protective immunity against most intracellular pathogens involves several arms of the immune response. A successful vaccine should also stimulate both protective cell-mediated immunity and specific antibody. Efforts should be directed toward making a vaccine that will stimulate the production of 1) more antibody, 2) more broadly cross-reactive neutralizing antibody (broadly neutralizing antibodies), and 3) antibody with a particular functional activity (antibody-dependent cell-mediated cytotoxicity; catalytic antibodies).