Clinical evidence indicates that a low level of high-density lipoprotein cholesterol (HDL-C) is a major risk of atherosclerosis. Raising HDL-C reduces this risk significantly, making HDL-C levels an important target of treatment for dyslipidaemia, especially in pre-existent atherosclerosis. HDL-C is protective against atherosclerosis, largely due to its function of reverse cholesterol transport. Additionally, some important roles include fibrinolysis, antioxidant functions, and reduction of platelet aggregability. A number of agents potentially modify HDL favourably. Niacin is the most potent HDL-C raising agent currently available in clinical practice, followed by fibrates. CETP inhibitors show greater HDL-C rising, but are still used in trial settings only. HDL mimetic agents are another group of agents that offer much promise. Clinical outcome data are awaited for these newer therapeutic agents.