In 1975, rapamycin, a macrolide produced by the bacterium Streptomyces hygroscopicus was first discovered and isolated from soil samples from Easter island. Although rapamycin was originally described as an antifungal agent, it was discovered that rapamycin has immunosuppressant activity, inhibiting T-cell proliferation, and that it suppressed incorporation of amino acids into cellular proteins, inhibiting protein translation. In 2009, Rapamycin was first shown to extend the lifespan of wild-type mice in 2009 by the National Institute on Aging Interventions Testing Program.

On Nov. 22, 2021, the U.S. Food and Drug Administration (FDA) approved sirolimus protein-bound particles for injectable suspension (albumin-bound) (Fyarro, Aadi Bioscience) for adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).