Several species of Leishmania cause human diseases that range from self-healing cutaneous lesions to fatal visceral leishmaniasis, mucosal leishmaniasis and diffuse cutaneous leishmaniasis. Drug resistance and toxicities associated with chemotherapy emphasize the need for a safe, effective vaccine. Studies of the immunopathogenesis and mechanisms of protective immunity define several features that should be met by an effective vaccine. The leishmaniases are unique among parasitic diseases because a single vaccine has the potential to protect against more than one species (disease) and be successful at both treating and preventing disease. In addition, several antigens have been identified and characterized that might be potential vaccine candidates. In this article, we focus on advances made with second-generation vaccines against leishmaniasis.