A growing number of cell-surface receptors are now being shown to generate signals that trigger the hydrolysis of sphingomyelin to release diffusible ceramides. Ceramides have been implicated as hey mediators in signaling pathways, with outcomes as diverse as cell proliferation, differentiation, growth arrest and apoptosis. The response depends on cell type, whether the signal is integrated with other signals originating from the same receptor and on the subcellular location of sphingomyelin hydrolysis and ceramide release.