Phospholipid flippases, are proteins able to translocate phospholipids from one side of a membrane to the other even against a gradient of concentration and thereby able to establish, or annihilate, a transmembrane asymmetrical lipid distribution. This lipid shuttling forms new membrane structures, in particular vesicles, which are associated with diverse physiological functions in eukaryotic cells such as lipid and protein traffic via vesicles between organelles or towards the plasma membrane, and the stimulation of fluid phase endocytosis. The transfer of lipids is also responsible for the triggering of membrane associated events such as blood coagulation, the recognition and elimination of apoptotic or aged cells, and the regulation of phosphatidylserine dependent enzymes. Exposure of new lipid-head groups on a membrane leaflet by rapid flip-flop can serve as a specific signal and, upon recognition, can be the cause of physiological modifications. Membrane bending is one of the mechanisms by which such activities can be triggered. We show that the lateral membrane tension is an important physical factor for the regulation of the size of the membrane invaginations. Finally, we suggest in this review that this diversity of functions benefits from the diversity of the lipids existing in a cell and the ability of proteins to recognize specific messenger molecules.