CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of Gram positive bacterial walls and malaria infected erythrocytes. CD36 expression on macrophages, dendritic and endothelial cells, and in tissues including muscle, heart, and fat, suggest diverse roles, and indeed, this is truly a multi-functional receptor involved in both homeostatic and pathological conditions. Despite an impressive increase in our knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This review focuses on CD36 in cardiovascular disease-what we know, and what we have yet to learn.