The use of mTOR inhibitors started about 30 years ago following the discovery of rapamycin, a macrolide derived from a soilborne microorganism Streptomyces hygroscopicus that exerts antibiotic, immunosuppressive and antiproliferative properties. Initially intended to be used as an antibiotic, a more detailed understanding of the mechanism of action of this class of drugs has rationalized and validated its use in the field of transplantation and oncology. Many clinical trials on mTOR inhibitors have been conducted in these two fields, in which urologists are actively involved. This review summarizes the current knowledge on the mechanism of action and clinical applications of mTOR inhibitors in renal transplantation and oncology.