In the past few decades, cDNAs for endothelial scavenger receptors that bind to negatively charged molecules, particularly acetylated low density lipoproteins (Ac-LDL), have been cloned by expression cloning using modified LDL as ligands. A prototypic members of endothelial scavenger receptor family, namely, scavenger receptor class B type I (SR-BI) has been characterized as a high density lipoprotein (HDL) receptor. Another prototypic member, CD36, has been determined as a multiple ligand receptor because it binds to oxidized LDLs (Ox-LDL), trombospondin, erythrocytes infected with Plasmodium falciparum, long-chain fatty acids, and Gram-negative and Gram-positive bacteria. Lectin-like oxidized LDL receptor-1 (LOX-1) has been discovered as the principal receptor that mediates the action of Ox-LDL in the vascular walls. Recently, the structure of oxidized phospholipids, originally found in Ox-LDL, and its molecular mechanism of action on endothelial cells were determined. Further, the use of genetically manipulated rodent models and the recent forward genetic screening technique revealed the physiological and pathological functions of these endothelial scavenger receptors in innate immunity and infection. In this review, the structure and function of these multiligand scavenger receptors of endothelial cells have been described mainly in relation with lipid metabolism.