INTRODUCTION: Leishmaniasis is a significant neglected tropical disease with limited treatment options that urgently requires ongoing efforts in drug discovery. Recent advances have focused on the development of new assays and methods to identify effective therapeutic candidates. AREAS COVERED: This review explores recent trends and methodologies in leishmaniasis drug discovery, with a particular focus on in silico and in vitro studies, as well as in vivo validation, using animal models. A detailed analysis of recent studies was provided, discussing the methodologies employed, such as manual and automated parasite quantification, and the use of fluorescence and luminescence-based techniques. Additionally, global research trends were analyzed, highlighting the leading countries in scientific output and the collaborative efforts driving advancements in this field. EXPERT OPINION: The field of leishmaniasis drug discovery has rapidly progressed in the last years, but the lack of standardized methodologies and limited in vivo validation remain significant hurdles. To advance promising treatments to clinical trials, cross-validation of preclinical findings and interdisciplinary collaboration are essential. Increased funding and global partnerships are also crucial to accelerate the discovery and development of alternative and effective therapies.