Earlier studies have shown that mTOR plays a key role in ribosome biogenesis. In bacteria, amino acids and ATP levels independently control ribosome biogenesis. Here, we describe recent findings demonstrating that homeostatic levels of amino acids, most notably branched-chain amino acids, and ATP, independently regulate the activity of mTOR. Unlike the effects of amino acids, the effects of ATP appear to be direct. Based on these findings we propose a model by which tumor cells existing in the anaerobic environment may have an advantage in growth by exploiting the rapid, although less efficient, production of ATP to drive growth via the mTOR signaling pathway.