Atherosclerosis is a condition where vascular smooth muscle cells (VSMCs), inflammatory cells, lipids, cholesterol and cellular waste accumulate in the inner lining of an artery, producing a fibro-fatty plaque and resulting in the thickening of the arterial wall. The tumor necrosis factor (TNF) family of cytokines plays a major role in the progression of atherosclerosis. Recently, TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, has been implicated in the development of atherosclerosis since it has been detected in normal and diseased atherosclerotic tissue. Not only is TRAIL involved in apoptosis and immune regulation, recent studies have provided a new function of TRAIL on vascular cells, such that TRAIL can promote endothelial cell (EC) and VSMCs migration and proliferation. In addition, TRAIL is implicated in regulating vascular tone. This review discusses our current understanding of TRAIL expression, regulation and function, and summarises the recent data implicating a role for TRAIL in atherosclerosis.