Leishmaniasis today constitutes a major health problem and a mammoth task in the field of drug discovery. This is due to the limited arsenal of effective anti-leishmanial chemotherapeutics, painful parenteral administration, exorbitant price and numerous adverse side effects associated with current clinically established leishmanicidal drugs. These include meglumine antimoniate (Glucantime®), stibogluconate (Pentostam®), liposomal amphotericin B (AmBisome®) and miltefosine. Also, due to the frequent manifestation of chemo-resistance in some countries, an exigent and relentless requisite is to develop innovative, innocuous and valuable anti-leishmanials. Metal compounds still offer excellent prospects for finding new ‘leads’ against parasitic diseases, including leishmaniasis. A number of organometallic compounds have already been evaluated in the therapeutic area to treat and eradicate leishmaniasis. In the last two decades, several new antimony-, bismuth-, tin-, tellurium-, palladium-, rhodium-, iridium-, ruthenium- and iron-based organometallic compound have been evaluated for their anti-leishmanial activity, showing great promise for the discovery of new anti-leishmanial drugs. This chapter outlines the old and new trends, and future perspectives for this exciting research field.