Oxygen is vital for life-sustaining aerobic respiration in humans and is arguably the most commonly administered drug in anaesthesia and critical care medicine. Within the mitochondrial inner membrane, oxygen acts as the terminal electron acceptor at the end of the electron transport chain whereby oxidative phosphorylation results in the synthesis of adenosine triphosphate (ATP), the coenzyme that supplies energy to all active metabolic processes. This article will discuss the key physiological concepts underpinning the movement of oxygen within the human body and also highlight some clinical applications that serve as examples of these concepts.