Mammalian cells depend on extracellular input for the regulation of growth, proliferation and survival. Cancer cells evade these requirements, and are able to take up nutrients in a cell-autonomous fashion, which allows continuous growth and proliferation. To fulfill the high bioenergetic demands imposed by transformation, tumors must develop alternative mechanisms of energy production. Accordingly, the biochemical signature of cancer cells involves a shift to aerobic glycolysis, also known as the "Warburg effect". This property of cancer cells has resulted of great utility in modern medicine for detection of early tumors by positron-emission scanning. Nonetheless, the underlying mechanisms and contribution of the Warburg effect to the malignant phenotype have remained obscure. Thanks to recent advances in cancer research, we are beginning to understand the link between cancer genetics and the abnormal use of glucose by tumors. A new scenario is thus emerging, in which bioenergetics would contribute to and sustain malignant transformation. These findings are not only important for a better understanding of tumorigenesis; tumor reliance on glycolysis can be exploited in the search for novel, more potent therapeutic approaches to cancer treatment.