Sirolimus (rapamycin) has evolved from a niche immunosuppressive agent used in organ transplantation into a versatile therapeutic platform with applications spanning rare genetic diseases, pulmonary disorders, vascular anomalies, oncology, and emerging geroscience. Through inhibition of the mechanistic target of rapamycin (mTOR), a central regulator of cellular growth, metabolism, proliferation, and aging, sirolimus exerts potent immunomodulatory, antiproliferative, and antiangiogenic effects. Over the past two decades, advances in understanding mTOR biology have transformed sirolimus from a transplant medication into a precision therapeutic for diseases driven by dysregulated cellular signalling. Clinical evidence now supports its use in lymphangioleiomyomatosis, tuberous sclerosis complex, vascular malformations, and selected neoplasms, while ongoing investigations explore its potential role in healthy aging, neurodegeneration, and autoimmune disorders. This review examines the pharmacology, molecular mechanisms, established clinical indications, safety considerations, and future therapeutic prospects of sirolimus in contemporary medicine.