The fundamental importance of Oxygen is well known for centuries, but how cells adapt to changes in Oxygen levels remains a mystery. William Kaelin, Jr., Sir Peter Ratcliffe, and Gregg Semenza unravelled this mystery for which they were awarded the Nobel prize for Physiology or Medicine in 2019. They discovered how cells can sense and adapt to changing oxygen availability. They identified the molecular machinery that regulates the activity of genes in response to different levels of Oxygen. In this article we will see a detailed account of the molecular mechanism of the cells in response to Normoxia and Hypoxia. This mechanism is one of life’s most essential adaptive processes. This discovery has established the basis of our understanding of how oxygen levels affect metabolism of the cells and physiological function. It has also paved the way for promising new strategies to fight anaemia, cancer and many other diseases.