Patient outcomes remain poor for advanced or metastatic soft tissue sarcomas (STS) and bone sarcomas despite a growing number of clinical trials involving single- and multi-agent chemotherapy. mTOR is an intracellular kinase that plays a central role in regulating cell growth, metabolism, survival and proliferation. mTOR inhibitors including temsirolimus, everolimus and ridaforolimus have demonstrated broad anticancer activity. Ridaforolimus is a non-prodrug analog of rapamycin (sirolimus) with conserved affinity for mTOR but improved solubility, stability and bioavailability when compared with sirolimus. Early clinical trials reveal a reproducible and predictable pharmacokinetic profile, a potent, rapid and prolonged target inhibition and an acceptable safety and tolerability profile. Phase II and III trials of ridaforolimus have produced promising clinical activity against advanced sarcomas and will be presented.