A significant fraction of cholesterol that accumulates in atherosclerotic lesions is actually oxidized to yield a number of derivatives, named oxysterols, which are provided with much stronger biochemical effects than the parental compound. Of note, an increasing bulk of studies is giving evidence of accumulation of oxysterols in a number of other chronic disease processes including quite common neurodegenerative diseases. In particular, defined cholesterol oxidation products, among those of main interest in pathophysiology, may strongly activate the mitochondrial pathway of apoptotic death. Modulation by oxysterols of various pro- and anti-apoptotic molecules involved in that pathway are hereafter examined under the light of the most recent relevant literature.