Sirolimus is an approved anti-rejection agent following liver or kidney transplantation that works through inhibition of the mammalian target of rapamycin (mTOR). As sirolimus functions through a pathway independent of calcineurin inhibition, it may have less potential for nephrotoxicity and carcinogenesis. That being said, there are a myriad of potential adverse effects reported with sirolimus, many of which are severe and unknown or poorly understood. Herein we present a case of sirolimus causing a serious but uncommon adverse event in an adult liver transplant recipient; the adverse event in this instance unfortunately resulted in significant medical testing and morbidity. The adverse event profile of sirolimus is summarized through review of available evidence.