Overall, the signalling effect/role of an individual SL could be defined on spatial-temporal basis with at least five parameters: (a) subcellular localisation, (b) regulation (c) chain length specificity, (d) kinetics of trafficking and (e) mechanism of action. For example, phosphorylation of 1–3% cytosolic SPH may double the levels of S1P that acts on G protein-coupled receptor (GPCR) to elicit a specific response in a particular cellular locality for certain period of time (Hannun & Obeid, 2008). Such signalling events can be described as a function of cytosolic S1P that is regulated by S1P Kinase, with the signal caused through the interaction of S1P with a GPCR. The elucidation of such complex systems remains challenging and a comprehensive discussion of the issue is beyond the scope of this review. However, an additional layer of significant complexity in terms of the pathogenic protozoa arises when considering the SL signalling network in the case of obligate intracellular parasites, where host SL biosynthesis, and its interaction with parasite de novo synthesis, must be taken into account.