Experimental, clinical and epidemiological researches have shown the incontestable causal relationship between low high-density lipoprotein (HDL) plasma concentrations and cardiovascular pathology on an atherosclerotic basis. Low HDL levels characterize about 10% of the general population and they represent the most frequent dyslipidemia in patients with coronary artery disease. Reduced HDL concentrations would be unable to effectively eliminate the cholesterol excess at the vascular wall, contributing to the inflammatory phenomena that characterize the pathogenesis of atherosclerosis since its initial phases. Results of numerous studies reasonably allow to suppose that HDL are able to exert, also directly, anti-inflammatory actions through the modulation of expression of diverse acute phase proteins. Although the today available therapeutic options aiming to increase HDL levels still show a modest effectiveness, in the experimental and pre-clinical field, the results of genetic investigations and pharmacological interventions have given more encouraging results, making nearer the possibility of treating this pathology concrete.