CD36 is a multispecific membrane glycoprotein that has been postulated to have a variety of functions. Evidence generated in isolated cells and in mice and rat models of altered CD36 expression has indicated an important role for CD36 in membrane transport of long-chain fatty acids. The cumulative data indicate that CD36 facilitates a major fraction of fatty acid uptake by muscle and fat, and that CD36 deficiency is associated with a large (60-80%) defect in fatty acid uptake by those tissues. In humans, polymorphisms in the CD36 gene may underlie defective fatty acid metabolism and some forms of heart disease. Herein we review our current understanding of the transport function and regulation of CD36. The realization that the transport step rate limits cellular fatty acid utilization suggests that abnormalities in CD36 expression or function may impact on susceptibility to certain metabolic diseases such as obesity and insulin resistance.