It has long been known that tumors depend on energy production pathways that are different from those of normal cells. These unique pathways require the expression and function of tumor-specific enzymes. Some of these glycolytic enzymes, as well as other modulators of tumor behavior, have recently been elucidated. In theory, inhibiting such enzymes or appropriately affecting such modulators should deprive tumors of energy, while leaving nontransformed cells unaffected. These factors include certain hexokinases that catalyze glycolysis in tumors and can be inhibited by 3-bromopyruvate. 2-deoxyglucose is another modulator that depletes hexokinase stores and cannot undergo further catabolism, thus depriving tumors of their energy source. Other enzymes or modulators are under scrutiny and have shown promise. Preliminary experiments on animals with hepatocellular carcinoma have indeed shown very encouraging results. It appears that modulating the energy production pathways of tumors is poised to become a substantial research area for cancer treatment. This review will focus on the energy production pathways of transformed cells, highlight the differences between transformed and normal cells in this regard and summarize recent experiments that take advantage of these disparities in cancer treatment.