Accumulating reports document the use by pathogens of cholesterol-enriched lipid microdomains, often called lipid rafts, as cell surface platforms to interact, bind and possibly enter into host cells. The challenge is now to understand what could be the functional role of these domains during pathogen invasion. Are they hijacked as general clustering devices for cellular binding sites and/or do they have other roles? In particular, is their cell signalling capacity activated and used by pathogens? In reverse, could lipid rafts activate bacterial mechanisms required for invasion? These issues will be discussed after an introduction on the current view on lipid rafts.