A critical feature in the biogenesis of cellular membranes is the translocation (flipping) of phospholipids and glycolipids from one leaflet of a membrane bilayer to the opposing leaflet. In some cases, flipping results in a pronounced transbilayer lipid asymmetry which has important functional consequences. In general, flipping occurs only very slowly in artificial membranes but is accelerated to a biologically relevant rate in some biomembranes. Current data suggest that this acceleration is most likely brought about by protein catalysts (termed flippases). This article reviews available information on flippases, including the recent isolation of two flippases operating at the plasma membrane of animal cells.