Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have well-recognized cardio-beneficial effects that include reductions in atherosclerotic lesions and mortality from myocardial infarction, stroke, and sudden cardiac death. In contrast, evidence suggests that more than 30,000 premature coronary deaths per year in the US alone are associated with consumption of high levels of trans isomers of unsaturated fatty acids, or trans fatty acids (TFAs). Epidemiological evidence from four large cohort studies overwhelmingly supports the conclusion that TFAs are linked to coronary heart disease (CHD). CHD in patients is associated with pathological vascular remodeling (PVR) and impaired compensatory vascular remodeling (CVR). PVR is characterized by thickening of vessel walls, reduction in elasticity, and occlusion of vessels, resulting in restricted blood flow. CVR represents a physiological process whereby vessels from a pre-existing arteriolar network develop into collateral arteries, effectively bypassing the site of arterial occlusion. The structure and function of vascular endothelial cell membranes are altered by both PVR and CVR. Oxidative stress and the induction of endothelial adhesion molecules promote PVR and inhibit CVR. It is known that n-3 PUFAs inhibit the release of soluble adhesion molecules and proinflammatory cytokines whereas TFA consumption has been linked to an increased release of these proinflammatory mediators. However, it is not known whether the changes in cell membrane composition induced by n-3 PUFAs or TFAs impact development of PVR and CVR directly or whether the changes result indirectly from altered expression and/or release of proinflammatory mediators. This review summarizes studies suggesting that n-3 PUFAs and TFAs have opposing effects on endothelial cells and that their effects on the endothelium might play an important role in vascular remodeling.