This article reviews the current understanding of the mechanism of action of the toxin, the clinical effects of ricin and abrin intoxication and how these relate to current and continuing prospects for vaccine development. The threat of bioterrorism worldwide has accelerated the demand for the development of therapies and vaccines against the ribosome-inactivating proteins. The diverse and unique nature of these toxins poses a challenge to vaccinologists. This paper will review the mechanism of toxicity and vaccines development to protect against the highly toxic plant-derived ribosomal toxins. Vaccine development is further complicated by the fact that as bioterrorism agents, abrin and ricin would most likely be disseminated as aerosols supplies. Our understanding of the mechanisms by which these toxins cross mucosal surfaces, and importance of mucosal immunity in preventing toxin uptake is only rudimentary. Research is now aimed at developing recombinant, attenuated vaccines based on a detailed understanding of the molecular mechanisms by which these toxins function. The evolution of the development of specific immunoprophylaxis of acute ricin poisoning from native toxoid to genetically engineered subunit vaccines based on the method of targeted mutagenesis is traced. The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine. These vaccines are discussed in the context of the toxicity and structure of ricin. In this review we summarize ongoing efforts to leverage recent advances in the design and use of vaccines.