High density lipoprotein (HDL) has two important roles: a) it modulates inflammation, and, b) it promotes reverse cholesterol transport. HDLcholesterol levels are inversely correlated with the risk of cardiovascular events. The main component of HDL, apolipoprotein AI (apo AI), is largely responsible for reverse cholesterol transport through the macrophage ATPbinding cassette transporter ABCA1. Apo AI can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acutephase response. Modification of the protein components of HDL can convert it from an antiinflammatory to a pro inflammatory and dysfunctional particle. Small peptides that mimic some of the properties of apo AI have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDLcholesterol levels. Endothelium is the interface between the blood and the extra vascular environment regulating the traffic of vital molecules between the blood and tissues. Oxidative stress and excess levels of reactive oxygen species disrupt the normal function of endothelium. HDL and other antioxidant/anti-inflammatory systems prevent endothelial dysfunction and maintain the critical balance needed for normal vascular function.