Infection with Leishmania parasites can cause disease across a range of clinical manifestations and outcomes. Given the practical difficulties in maintaining vector control programs, vaccination is likely the only way in which the sustained reduction or elimination of the leishmaniases can be achieved. In this review, we focus on the development of second-generation vaccines with emphasis on defined subunit vaccines using recombinant expression techniques. We highlight particular antigens that have provided protection in animal models, and discuss methods, such as inclusion in chimeric fusion proteins and use of appropriate adjuvants, that are likely required to transition these into clinically-relevant candidates. We also outline the alternative strategies, such as attenuated parasites, DNA vaccination, and use of sand fly proteins, that are being proposed.