Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that controls a wide range of growth-related cellular processes. In the past several years, many factors have been identified that are involved in controlling mTOR activity. Those factors in turn are regulated by diverse signaling cascades responsive to changes in intracellular and environmental conditions. The molecular connections between mTOR and its regulators form a complex signaling network that governs cellular metabolism, growth and proliferation. In this review, we discuss some key factors in mTOR regulation and mechanisms by which these factors control mTOR activity.