The production of recombinant proteins is a rapidly expanding industrial field. Several proteins that previously were extracted from their natural source by expensive and time-consuming processes can now be produced in various organisms, including bacteria, yeast, insect cells, and mammalian cells. These traditional systems have their advantages and disadvantages, but one of the major problems is related to post-translational modifications that mostly differ from those in mammals. The LEXSY system was developed for the expression of recombinant proteins in Leishmania tarentolae a non-pathogenic protozoan species isolated from the lizards Tarentolae annularis and Tarentolae mauritanica it is a biosafety level I protist with high biomass production that is well-suited for cultivation on an industrial scale. The system has advantages for the expression of several proteins, including glycosylated proteins, and for the homogenous glycosylation of mammalian proteins. In this review, we have compared the classical systems and LEXSY, and presents a historical review of heterologous expression in Leishmania. We also list the specific characteristics, advantages, and problems with LEXSY in a work-oriented perspective to facilitate the use of this eukaryotic expression platform.