This chapter reviews the methods that are most useful to study the role of CoQ and its reductases in the regulation of liver plasma membrane SMase (nSMase). Ceramide has received much attention, because an increase in ceramide levels initiates cellular responses for cell growth, differentiation, stress, and apoptosis. SMase, which is an integral plasma membrane protein, is related to apoptosis triggered by stress-inducing agents. Although a role for the aSMase in cell signaling has been questioned, the nSMase is apparently the most important in ceramide signaling according to the number of agents stimulating this enzyme and its favorable position at the plasma membrane, where sphingomyelin is highly concentrated. Plasma membrane contains an electron transport system that reduces coenzyme Q (CoQ) in this membrane, which guarantees its antioxidant properties but also mediates the regeneration of other primary antioxidants such as ascorbate and α-tocopherol. Coenzyme Q seems to be the central component of this plasma membrane redox system and also the key factor in preventing apoptosis triggered by externally induced oxidative stress. Ceramide can also induce cell death after its intracellular accumulation by activating proteases of the caspase family such as caspase. It is an important lipid-signaling molecule because its intracellular accumulation triggers cell-growth arrest and cell death. This sphingomyelin is an abundant component of the outer leaflet of the plasma membrane bilayer, and it is the most important candidate to be the source of ceramide as a consequence of an externally induced oxidative stress.