Ceramide is one of the major sphingosine-based lipid second messengers that is generated in response to various extracellular agents. However, while widespread attention has focused on ceramide as a second messenger involved in the induction of apoptosis, important issues with regard to the mechanisms of ceramide formation and mode of action remain to be addressed. Several lines of evidence suggest that ceramide and oxidative stress are intimately related in cell death induction. This review focuses on the putative relationships between oxidative stress and sphingolipid metabolism in the apoptotic process and discusses the potential mechanisms that connect and regulate the two phenomena.