Over 100 years ago Otto Warburg observed that proliferating cells including cancer cells rely on inefficient aerobic glycolysis for energy generation instead of using the more efficient oxidative phosphorylation in mitochondria. To this day, it remains enigmatic why, and scientists have been argueing about it for many decades. The american biochemist Jason Cantor and his team now made an important observation: It is not about the amount of energy generated but about spatial organization. At the centre sits the enzyme hexokinase (HK), that is crucial for the first step of glucose metabolism. In non-proliferating cells it is attached to mitochondria, supplying them with pyruvate, an early product of glucose metabolism. Cancer cells and other proliferating cells rely on cytosolic HK1 and ferment glucose to lactate to produce energy where it is needed for proliferation. Most cancer cells use a second form of HK (HK2), that is detached from mitochondria under physiologic conditions. The study adds important mechanistic details to the discussion around the Warburg-Effect. More importantly, it identifies HK2 as a potential target for cancer therapy.