In eukaryotic cells, the biological membrane is characterized by a non-uniform distribution of membrane lipids, vertically as well as laterally. The paradigm for the vertical non-random distribution is the plasma membrane, where phosphatidylcholine (PC), sphingomyelin (SM), and glycosphingolipids are primarily located on the exoplasmic leaflet, while aminophospholipids, including phosphatidylserine (PS) and phosphatidylethanolamine (PE), are generally enriched in the cytoplasmic leaflet. Other minor phospholipids, such as phosphatidic acid and phosphatidylinositol (PI), are also enriched on the cytoplasmic face. Such asymmetrical distribution is related to each lipid regulating various biological events through interaction with other molecules. The clarification of the regulatory mechanism of the distribution and movement of membrane lipids is crucial to understanding the physiological roles of lipids. Here we focus on PS, which has been reported to be involved in apoptosis, blood coagulation and other biological phenomena, and summarize the present understanding of the dynamics of this phospholipid, including biosynthesis, metabolism, transport, and transbilayer movement. We also refer to diseases that have been reported to be related to phospholipid asymmetry.