Leishmaniasis causes significant morbidity and mortality worldwide, constituting an important public health problem. Leishmania infections cause a wide spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Attempts to develop an effective vaccine to control leishmaniasis have been shown to be feasible, but no vaccine is in active clinical use. The ability to create genetically modified parasites by eliminating virulence or essential genes is considered a powerful alternative in the development of an effective protective vaccine. Here, recent findings related to genetically defined live attenuated Leishmania parasites as promising vaccine candidates are reviewed.