Learning from the successes of other vaccines that enhance natural and existing protective responses to pathogens, the current effort in HIV vaccine research is directed toward inducing cytotoxic responses. Nevertheless, antibodies are fundamental players in vaccine development and are still considered in the context of passive specific immunotherapy of HIV, especially since several broadly neutralizing monoclonals are available. Special interest is directed toward antibodies binding to the glycan array on gp120 since they have the potential of broader reactivity and cross-clade neutralizing capacity. Humoral responses to carbohydrate antigens have proven effective against other pathogens, why not HIV? The variability of the epitope targets on HIV may not be the only problem to developing active or passive immunotherapeutic strategies. The dynamics of the infected immune system leads to ambiguous effects of most of the effector mechanisms calling for new approaches; some may already be available, while others are in the making.