Otto Warburg discovered that cancer cells exhibit a high rate of glycolysis in the presence of ample oxygen, a process termed aerobic glycolysis, in 1924 (Warburg et al., 1924). Since then we have significantly advanced our understanding of cancers’ fuel choice to meet their demands for energy and for the production of biosynthetic precursors. In this review, we will discuss the preferred nutrients of cancer cells and how they are utilized to satisfy their bioenergetic and biosynthetic needs. In addition, we will describe how cell intrinsic and extrinsic factors such as oncogene mutations, nutrient and oxygen availability and other microenvironmental factors influence fuel choice.