Purpose of reviewRecent publications have focused on the results of multicenter trials and single-center reports detailing the use of Sirolimus (SRL) and Everolimus in organ transplantation and coronary artery disease. This review will define the current role of SRL.Recent findingsMulticenter randomized trials have demonstrated the efficacy of SRL in kidney and kidney–pancreas transplantation with minimization or elimination of cyclosporine, or, along low doses of tacrolimus. The efficacy of SRL–mycophenolate (MMF)–corticosteroids regimens in kidney transplantation has been demonstrated in single-center reports. In phase III trials, Everolimus is more efficacious than MMF and azathioprine in kidney and heart transplantation, respectively. Everolimus and Sirolimus–impregnated coronary artery stents have lower restenosis rates and a lower incidence of cardiac events than regular stents. Toxicities of SRL are concentration related, and improve with control of SRL levels. Hepatic artery thrombosis and bronchial anastomosis dehiscence are fatal complications needing further research.SummarySirolimus is being used more commonly as an immunosuppressive agent in all organ transplants. Everolimus is still awaiting Food and Drug Administration approval. This review describes the current role of Sirolimus, and use in combination with other immunosuppressive agents.