Ceramide can be formed either by a catabolic pathway, from the hydrolysis of membrane sphingomyelin, or by de novo biosynthesis, starting from the condensation of serine with palmitate in the endoplasmic reticulum. Ceramide and its bioactive metabolite S1P mediate several inflammatory, proapoptotic and nociceptive signalling cascades. S1P can cross the plasma membrane through either non-specific ABC transporters or through the recently discovered Spinster 2 (SPNS2) transporter, which is specific for S1P. S1P signalling is mediated by five G-protein coupled receptors (S1PR1-5). CDase, ceramidase; CerS, ceramide synthase; SMase, sphingomyelinase; SMS, sphingomyelin synthase; SphK, sphingosine kinases; SPL, S1P lyase; SPPase, sphingosine phosphate phosphatase; SPT, serine palmitoyltransferase.