One of the characteristics of ceramide-mediated biology is the variety of biological outcomes observed in response to its intracellular accumulation. The molecular mechanisms that govern the cell "decision-making" in response to ceramide remain largely unclear. In this perspective, the study of neural models has begun to provide important insight into the understanding of these mechanisms that regulate differentiation and cell death. Indeed, differentiation and cell death are among the most common effects elicited by ceramide in most cell types and in neural cells, too. Therefore, the lessons we may learn from the study of ceramide regulation of neurobiology would also shed light on the regulation of ceramide-mediated biology in other cellular models. Since increasing evidence links aberrant metabolism of ceramide to different pathologies, the understanding of the mechanisms underlying these events may represent the key to the design of novel therapeutic approaches.