The study of normal mammalian cell growth and the defects that contribute to disease pathogenesis links metabolism to cell growth. Here, we visit several aspects of growth-promoting metabolism, emphasizing recent advances in our understanding of how alterations in glucose metabolism affect cytosolic and mitochondrial redox potential and ATP generation. These alterations drive cell proliferation not only through supporting biosynthesis, energy metabolism, and maintaining redox potential but also through initiating signaling mechanisms that are still poorly characterized. The evolutionary basis of these additional layers of growth control is also discussed.