A number of human diseases are linked to local reduced oxygen availability. Hypoxemia, the condition in which oxygen partial pressure in blood falls below 40 mmHg, generates a distress which leads the cells in the vascular wall to activate a genetic program inducing a homeostatic response. The effectiveness of this response is conditioned by the degree and duration of the hypoxic stress and depends on the equilibrium among several factors which are worked out mainly in the vascular endothelial cell layer. Among them are vasoconstrictors such as angiotensin II, endothelins, prostaglandins and thromboxans, and vasodilators such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. A present challenge of the research is understanding the physiological and pathophysiological relevance of the growing body of data collected, disclosing the potential therapeutical application of the basic knowledge in this field.