Endothelial lipase, which is a newly identified member of the lipase family, plays an important role in high-density lipoprotein metabolism, which catalyzes the hydrolysis of high-density lipoprotein phospholipids and facilitates the clearance of high-density lipoprotein from the circulation. In addition, inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), upregulate endothelial lipase expression, and endothelial lipase also affects the expression of cytokines, which in turn play an important role in atherogenesis. Endothelial lipase expression has been associated with macrophages within human atherosclerotic lesions. However, an important challenge is to determine how endothelial lipase alters the progression of atherosclerosis. Although few data are available from human studies, it seems that plasma endothelial lipase levels in individuals with atherosclerosis might be higher than that measured in healthy individuals. Therefore, we believe that endothelial lipase might be a promising marker for atherosclerosis in clinical settings in the future.