As detailed in this review, there have been considerable advances in DNA vaccines against Leishmania and T. cruzi in recent years. Taken together, these studies clearly validated the concept of using DNA vaccines for both protection and therapy against these protozoan parasites in a variety of mouse models. While sterile immunity seems to be an irrealistic goal for either Leishmania or T. cruzi, a reduction in disease severity and in the development of the pathology seems clearly within the reach of DNA vaccines. Nonetheless, the relevance of such mouse models for the development of veterinary or human vaccines against these parasites has been challenged by some authors. The few DNA vaccine studies in nonmurine models of leishmaniasis suggest that some extrapolation may be feasible, but certainly not completely. Additional advanced preclinical studies of DNA vaccine candidates in nonmurine animal models such as rats, hamsters, dogs, or monkeys are thus warranted in the next few years, to further explore the immunology and efficacy of DNA vaccines against these parasites. As already observed in such studies for other pathogens, this will lead to the challenge of achieving in these species an immunogenicity of comparable level and protective efficacy as that obtained in murine models. However, advances in adjuvants, DNA vaccine formulation, and delivery systems are likely to contribute to such results [1, 109] .