The protein mammalian target of rapamycin (mTOR) plays a central role in cell growth and proliferation. Excessive mTOR activity is a prominent feature of many neoplasms and hamartoma syndromes, including lymphangioleiomyomatosis (LAM), a destructive lung disease that causes progressive respiratory failure in women. Although pharmacological inhibitors of mTOR should directly target the pathogenesis of these disorders, their clinical efficacy has been suboptimal. Recent scientific findings reviewed here have greatly improved our understanding of mTOR signaling mechanisms, provided new insights into the control of cell growth and proliferation, and facilitated the development of new therapeutic approaches in LAM, as well as other neoplastic disorders that exhibit excessive mTOR activity.