Ceramide is a sphingosine-based lipid signaling molecule that regulates cellular differentiation, proliferation, and apoptosis. The emerging picture suggests that coupling of ceramide to specific signaling cascades is both stimulus and cell-type specific. Ceramide action is determined within the context of other stimuli and by the subcellular topology of its production. Here, we discuss the pathways of ceramide generation and the interaction of ceramide with caspases and other apoptotic signaling cascades.