Organisms maintain a complex relationship between the production of oxidative radicals and endogenous antioxidant levels and antioxidant enzymatic activities. Apart of its bioenergetics role in mitochondria, CoQ10 is also present in the rest of cell membranes and in plasma lipoproteins. In these structures, CoQ10 plays a key antioxidant role, preventing lipidic oxidative damage and regulating enzymatic and regulatory activities. Many years ago, two essential CoQ10-dependent dehydrogenases were characterized, cytochrome b5 reductase and NQO1. These enzymes are able to maintain a redox cycle of CoQ10 in membrane, preventing oxidative damage and maintaining other antioxidant systems depending on ascorbic acid and α-tocopherol. Recently, other CoQ10-dependent enzymes such as a mitochondrial dehydrogenase (FSP1) and a dehydrogenase associated with the outer leaf of the plasma membrane have increased the importance of CoQ10 in the prevention of oxidative damage and the regulation of apoptosis. The role of these enzymes in aging remains to be clearly determined but CR, a known prolongevity procedure, increases the activity of CoQ10-dependent dehydrogenases and prevents oxidative damage associated with aging. Then, maintenance of the activity of these extramitochondrial CoQ10-dependent activities seems to be important for aging and longevity. This work was supported by grants from the Instituto de Salud Carlos III.