Clinical, experimental and epidemiological research has shown the undeniable causal relationship between low HDL plasma concentrations and cardiovascular disease. Low HDL levels are present in about 10% of the general population and represent the most frequent form of dyslipidemia in patients with coronary disease. Reduced HDL concentrations seem to be unable to eliminate efficiently the cholesterol excess at vascular wall level, contributing to the onset of the inflammatory response that typically occurs in the pathogenesis of atherosclerosis right from its earliest stages. The results of numerous studies quite convincingly suggest that HDL is capable of exerting anti-inflammatory activity either directly or by modulating the expression of a number of acute phase proteins. Although the therapeutic options currently available for raising HDL levels still show modest efficacy, both in experimental and pre-clinical fields, genetic investigation and specifically aimed pharmacological treatment have produced more encouraging results, shedding some light on the concrete possibility of being able to treat this disease in the very near future.