Abstract: Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one leaflet to the other and thereby help generate membrane lipid asymmetry. Among these ATP-driven transporters, the P4 subfamily of P-type ATPases (P4-ATPases) comprises lipid flippases that catalyze the translocation of phospholipids from the exoplasmic to the cytosolic leaflet of cell membranes. While initially characterized as aminophospholipid translocases, recent studies of individual P4-ATPase family members from fungi, plants, and animals show that P4-ATPases differ in their substrate specificities and mediate transport of a broader range of lipid substrates. At the same time, the cellular processes known to be directly or indirectly affected by this class of transporters have expanded. Current concepts suggest that the dynamic process of lipid translocation may help drive membrane bending and vesicle budding. This lecture summarizes recent progress on the identification and characterization of the various lipid flippases and the demonstration of their biological functions.