The biogenesis of high density lipoproteins (HDL) is a complex process and involves several membrane proteins and plasma proteins. apoA-Ⅰ is the major structural and functional protein in HDL. apoA-Ⅰ can activate lecithin/cholesterol acyltransferase (LCAT) and poor-lipid apoA-Ⅰ is the important receptor for ATP-binding cassette transporter A1 (ABCA1)-mediated efflux of cholesterol in macrophages. So, apoA-Ⅰ plays an important role in the metabolism of HDL and cholesterol and endows HDL with multiple anti-atherogenic activities. This review focuses on the roles of apoA-Ⅰ in biogenesis of HDL, in order to provide the new thought for revealing mechanisms of HDL metabolism.