Around the world, approximately 5 million people became infected with HIV in 2001, an estimated 70% via sexual transmission. Numerous studies have demonstrated that it is difficult to achieve total protection from vaginally or rectally acquired HIV / SIV when using parenteral immunization. Mucosal immunization was seen as the best approach to achieve sustainable immune responses at mucosal sites of viral entry. This was further emphasized when several studies implicated rectal and vaginal mucosa as latent reservoirs for the HIV virus and virus-specific CD8+ T cell immune responses in gastrointestinal mucosa were shown to be less efficient than in systemic tissues. Mucosal vaccines utilizing various routes of immunization including intranasal, intrarectal, intravaginal and oral immunization have been tested for their potency to induce virus-specific immune responses systemically but especially at mucosal sites of viral entry. The unsatisfactory results in initiating simultaneously sufficient immune responses at mucosal and systemic sites are being overcomed by use of appropriate and novel adjuvants such as Cholera toxin, Escherichia coli heat-labile toxin, immunostimulatory CpG motifs, coinjection of cytokines and others. Various routes of immunization are now being compared and combinations of mucosal immunization and parenteral boost and vice versa have also been tested. Generations of new vaccines, such as DNA-based vaccines, multipeptide, lipopeptide and alphavirus replicon particles-based vaccines have been created and studied for their efficiency.