The role of ethanol in human health and nutrition is complex. Ethanol is a macronutrient energy source, capable of providing calories for all of the essential biological activities of the human organism: replication, function and maintenance of individual cells; energy for physical work; and thermogenesis. Ethanol differs from the other principal dietary macronutrient energy sources, glucose, fatty acids, and amino acids in two fundamentally important ways. First, although each of the other classes of energy compounds has a macromolecular storage form glycogen (glucose), lipids (fatty acids), and protein (amino acids)], there is no storage form for ethanol. Second, fuel consumption in multicellular organisms is coordinated and prioritized largely through the regulation of entry of the energy source into the cell. For sugars, fatty acids, and amino acids, this transport across the plasma membrane is mediated by proteins thus providing an easy mechanism of regulation. In contrast, ethanol freely diffuses across plasma membranes, not requiring protein-mediated transport. These properties of ethanol define its unique role and hierarchal position as a macronutrient in human nutrition. While chronic, excessive consumption of ethanol leads to disease, low to moderate consumption has been shown to reduce risk of certain high incidence diseases. Numerous epidemiological studies have documented that a reduced risk of coronary heart disease usually accompanies regular consumption of a moderate level of ethanol[. It has also recently been reported that ethanol consumption reduces the risk of development of adult onset or Non-Insulin Dependent Diabetes Mellitus (NIDDM), The protective effect of dietary alcohol has been attributed to the increase in HDL cholesterol and associated apolipoproteins. However, the effect of alcohol on HDL and lipoproteins does not fully account for the protective role of dietary ethanol. Therefore, ethanol must have other important effects in human metabolism. increased risk of both coronary heart disease and NIDDM has recently been shown to be associated with increased risk of several other diseases, each of which has insulin resistance as an underlying cause. Insulin resistance results in a progressive cascade of abnormalities associated with macronutrient fuel metabolism. This metabolic derangement was first described by Reaven and termed ''Syndrome X.'' The explanation of the health-promoting effects of moderate ethanol consumption may lie in part in ethanol's role as a macronutrient energy source and in its ability to affect the onset, development and progression of Syndrome X. This review will describe our current level of understanding of ethanol metabolism and its effects on the metabolism of other macronutrient energy sources and will discuss the possible role of ethanol in Syndrome X and reduced risk of coronary heart disease.