The concentration of high density lipoprotein cholesterol (HDL-C) has been found to be a powerful negative predictor of premature coronary heart disease (CHD) and stroke in human prospective population studies. Evidence of the protective properties of HDLs has also been documented in the elderly and their offspring. HDLs mediate several functions that provide an insight into their potential anti-atherogenic mechanisms. Intervention strategies to prevent CHD have generally focused on lowering low-density lipoprotein cholesterol (LDL-C). However, several lifestyle and pharmacological interventions have the capacity to raise the level of HDL-C. As data accumulate on the protective role of HDLs, there is growing support for interventions that act to raise HDL-C concentrations.