 Cancer is a metabolic disease that involves the uncoupling of glycolysis from oxidative phosphorylation in the tricarboxylic acid cycle, leading to high-rate glycolysis and the Warburg effect, which are crucial for cancer cell proliferation. The review discusses the molecular events involved in this process and highlights the key role of the hypoxia-inducible transcription factor HIF-1 in long-term adaptation to hypoxia. Advanced anti-cancer treatments targeting tumor glycolysis are briefly reviewed. This article was authored by Palo Iporparato, Rajesh K. Dedeach, Suvira E. Dup, and others.