The use of plants as production systems for vaccine antigens has been actively investigated over the last 15 years. The original research focused on the value of this expression system for oral delivery based on the hypothesis that plant-expressed antigens would be more stable within the digestive tract and would allow for the use of the oral route of administration to stimulate a mucosal immune response. However, while first conceived for utility via the oral route, plant-made antigens have also been studied as classical immunogens delivered via a needle to model animal systems. Antigens have been expressed in a number of whole plant and cell culture systems. Several alternative expression platforms have been developed to increase expression of antigens or to elicit preferred immunological responses. The biotechnological advances in plant expression and the immunological testing of these antigens will be reviewed in this paper focusing primarily on diseases of livestock and companion animals.