Although educational programs have had some impact, immunization against HIV will be necessary to control the AIDS pandemic. To be effective, vaccination will need to be accessible and affordable, directed against multiple antigens, and delivered in multiple doses. Plant-based vaccines that are heat-stable and easy to produce and administer are suited to this type of strategy. Pilot studies by a number of groups have demonstrated that plant viral expression systems can produce HIV antigens in quantities that are appropriate for use in vaccines. In addition, these plant-made HIV antigens have been shown to be immunogenic. However, given the need for potent cross-clade humoral and T-cell immunity for protection against HIV, and the uncertainty surrounding the efficacy of protein subunit vaccines, it is most likely that plant-made HIV vaccines will find their niche as booster immunizations in prime-boost vaccination schedules.