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Several decades ago, scientists showed the existence of a hemoprotein implicated in the metabolism of foreign and endogenous compounds. This enzyme was further shown to be part of a superfamily named cytochrome P450 (CYP450). Today, this family comprises more than 150 different isoforms distributed among multicellular organisms such as animals, vegetables as well as fungi. CYP450 is implicated in the metabolism of lipids, steroids, vitamins, bile acids, prostaglandins and many other endogenous molecules. Thus, it is essential for homeostasis. But CYP450 does much more than that. It is directly implicated in the elimination of toxic substances which can interfere with body functions if they accumulate. CYP450 plays also a key role in the acquisition of toxic characteristics by some xenobiotics like heterocyclic aromatic amines that are metabolized to carcinogenic products. Finally, studies of the CYP450 enlighten its outstanding participation in the metabolism of numerous drugs that are used in modern medicine. Recently, CYP450 research has focussed on its role in the pathophysiology of common diseases, particularly cancer and hypertension. Here, we exhaustively review certain diseases where CYP450 is either modified by a particular clinical situation, or implicated in the pathophysiology. Thus, senior authors have reviewed the current knowledge on the impact of liver diseases, inflammation, hypoxia and stroke on the activity of CYP450 and, consequently on the metabolism of various molecules. The direct or indirect implications of CYP450 in the pathophysiology of several conditions such as hypertension, cancer, and brain dysfunction are also review.