Historical perspectives Epidemiological studies demonstrate a clear inverse association of HDL with cardiovascular disease. Results from the Framingham Heart Study demonstrate that low levels of HDL are an independent risk factor for coronary heart disease (CHD). Statins, which can reduce levels of apoB-containing lipoproteins and plasma cholesterol levels, have been only partially successful at reducing the risk of CHD, while 70% of the problem remains to be solved. In addition, with the increasing prevalence of metabolic syndrome, in order to successfully address the prevailing CHD problem, there is a need for an alternate mode of therapy than simply to reduce plasma cholesterol levels. Thus, much recent attention has focused on studying HDL as an alternate therapy. Badimon et al. showed that administering human HDL to cholesterol-fed rabbits regressed atherosclerotic plaque formation [1]. Since apoA-I is the major protein component of HDL, studies with isolated apoA-I in the presence of lipid have been performed [2], termed recombinant HDL therapy. Transgenic expression of human apoA-I in athero sclerosis-sensitive mouse models also demonstrated significant inhibition of atherosclerosis [3]. The field got a boost when apoA-I milano –lipid complexes (40 mg/kg of protein) were infused in humans and the results were followed by intravenous ultrasound. When apoA-I milano –POPC complexes were infused in 40 patients, there was a significant decrease in the atheroma volume (between 3.5 and 5%) compared with baseline as studied by intravenous ultrasound [4]. However, perhaps due to the prohibitive cost of producing human or recombinant apoA-I, this technology has not