The lung is both the conduit for oxygen uptake and is also affected by hypoxia and hypoxia signaling. Decreased ventilatory drive, airway obstructive processes, intra-alveolar exudates, septal thickening by edema, inflammation, fibrosis, or damage to alveolar capillaries will all interpose a significant and potentially life-threatening barrier to proper oxygenation, therefore enhancing the alveolar/arterial pO 2 gradient. These processes result in decreased blood and tissue oxygenation. This review addresses the relationship of hypoxia with lung development and with lung diseases. We particularly focus on molecular mechanisms underlying hypoxia-driven physiological and pathophysiological lung processes, specifically in the infant lung, pulmonary hypertension, and chronic obstructive pulmonary disease.Keywords Hypoxia . Lung . Pathology . HIF Air, containing oxygen at approximately 21% partial pressure at sea level (140-150 mmHg), travels through up to 20 generations of airways by mass flow and then diffuses into the gas exchange units (alveoli) in the lung with a partial pressure of approximately 105-110 mmHg. The human lung contains approximately 480 million alveoli, which represent 64% of total lung structure. These alveoli are elegantly packed in only 1.3-2.6 L of total lung volume, providing a surface area of 120-150 m 2 , equivalent to the dimensions of a "tennis court" dedicated for gas exchange. Although the molecular determinants of lung size are not known, oxygen diffusion constant and gas exchange surface area are roughly proportional to body weight and oxygen consumption in different species [1]. Physical hyperactivity and exposure to a cold environment or high altitude lead to increased oxygen diffusion capacity, in proportion to enhanced oxygen consumption [1].Decreased ventilatory drive, airway obstructive processes, intraalveolar exudates, septal thickening by edema, inflammation, fibrosis, or damage to alveolar capillaries will all interpose a significant and potentially life-threatening barrier to proper oxygenation, therefore enhancing the alveolar/ arterial pO 2 gradient. This review addresses the contribution of hypoxia to lung diseases and the potential molecular mechanisms involved in hypoxia-driven physiological and pathophysiological lung processes (Fig. 1), particularly in the infant lung, pulmonary hypertension, and chronic obstructive pulmonary disease. The fundamental concepts underlying hypoxia-induced gene expression and the molecular regulation of HIF(s) also apply to the lung, and they will be cited in relation to their demonstrated role in lung physiology or pathophysiology.