Among all gases, oxygen is the most known, most extensively used gas in clinical setting. Hypoxia is a condition in which the body as a whole (generalized hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply. However, aside from its many detrimental effects on organisms, hypoxia may also exerts its beneficial effects on individuals through a mechanism known as preconditioning. In this literature review, we sought to examine the historic aspect, several possible underlying molecular mechanisms, and clinical application perspective to ”hypoxic preconditioning”