Oral vaccines offer significant advantages over needle-based vaccines for achieving universal childhood vaccination goals. The expression of vaccine antigens in transgenic plants has the potential to provide a convenient, safe approach for oral vaccination and thus a feasible alternative to traditional parenteral vaccines. Many developments in the field have ushered in improvements such as enhanced protein antigen expression for the use of plants as factories for vaccine production, and facilitated studies pertaining to immunogenicity of candidate vaccines. Oral delivery of plant-based vaccines offers the benefit of antigen protection within the harsh intestinal environment. Within the gut, mucosal immune cells are poised to respond to pathogens, but can also be exploited to elicit protective immune responses to oral vaccines. Inclusion of mucosal adjuvants during immunization with the vaccine antigen has been an important step towards the success of plant-based vaccines. This review discusses the mechanisms that control mucosal immune responses and highlights some of the studies and the results achieved following immunization with transgenic plants.