Over the last 2 decades, the number of emergent infectious diseases has increased at an alarming rate. Also disheartening is the rise of known infectious pathogens that have acquired extensive drug resistance and reemerged with greater virulence. More recently, the threat of bioweapons has rekindled an urgency for the development of mass immunization programs. In response to this increased infectious disease threat, efforts have been intensified to identify more effective, inexpensive, and more easily deliverable mucosal vaccination methods. One area of research currently under development is the genetic modification of plants for production of immunoprotective proteins. The ability of plants to synthesize complex proteins using the elements of sunlight, soil, air, and water makes them ideal organisms for harvesting large quantities of therapeutic proteins. The introduction of antigen or antibody encoding genes into the genome of a plant through stable transformation enables them to manufacture vaccine proteins that are directly applicable for use in disease treatment, unlike yeast, bacterial, insect or other expression systems that require purification steps before delivery. As an alternative to stable transformation, plants can be used to generate large quantities of vaccines by acting as hosts for genetically altered plant viruses in which antigen proteins can be expressed and later purified from infected plant tissues. In this review, we survey current experimental strategies for using edible plants to achieve passive and active immunization against infectious disease organisms. In addition, methods are described for the construction of transformed plants that can provide protection against autoimmune diseases. Concerns and present obstacles to effective immunization with plant-based vaccines for animals and humans are presented.