Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. However, its clinical application is often hampered by poor aqueous solubility, first-pass metabolism, transport by p-glycoprotein efflux pump, limited oral bioavailability and nonspecific distribution in off-target sites. Recently, various formulation strategies have emerged to overcome these limitations. Among these, pharmaceutical nanotechnology with numerous advantages has great potential for sirolimus delivery. Up to now, the only nanoparticle based FDA approved formulation in the market is Rapamune^® tablet which is composed of drug nanocrystals. This review focuses on recent studies that have been investigated various nanostructured carriers such as liposomes, micelles, polymeric nanoparticles, nanocrystals, magnetic nanoparticles, albumin nanoparticles, solid dispersion nanoparticles and niosomes for sirolimus delivery (in organ transplantation, cancer, vascular restenosis, etc.).