High plasma triacylglycerol (triglyceride, TG) levels is a risk factor for atherosclerosis. Very large lipoproteins, such as chylomicrons, alone are not considered atherogenic, but TG-rich remnant lipoproteins can penetrate into the vascular wall. Importantly, accumulating evidence suggests that all TG-rich lipoproteins stimulate cytokine expression in circulating monocytes. Very low-density lipoprotein (VLDL) stimulates monocyte adhesion to endothelial cells and expression of inflammatory genes in macrophages. Furthermore, fatty acids released from large lipoproteins can stimulate both vascular cells and circulating monocytes. It is likely that fatty acids released from TG-rich lipoproteins contribute to atherogenesis, but the role of fatty acids in ischemic heart disease is not as direct as that of cholesterol. Fatty acids influence plasma lipoprotein levels and either stimulate or suppress numerous cellular functions relevant to atherogenesis. While certain n-3 fatty acids are good for health, most other medium- to long-chain fatty acids appear to promote inflammation in cell culture studies and need to be studied further. Nevertheless, the existing evidence supports the general conclusion that TG-rich lipoproteins and fatty acids greatly accelerate the progression of atherosclerosis. This may be because of their inflammatory effects.