The existing work demonstrates that striking differences exist between men and women in lipid kinetics. These differences cannot be explained simply by the presence and action of sex hormones and are not always due to secondary, phenotypic traits that characterize men and women (e.g., body-composition, regional fat distribution). In fact, some of these secondary traits may even be the result of sexual dimorphism in metabolism, and being of female or male genotype also determines intermediary metabolism. This review provides an overview of the currently available information regarding sexual dimorphism in human lipid metabolism but does not provide an in-depth account of current knowledge (due to limited space); it will be a broad introduction to those interested in the field and will, hopefully, stimulate further efforts to unravel the secrets of male and female metabolism. What has been discovered so far regarding differences in lipid metabolism between men and women is likely only the tip of the iceberg; clearly, more work is necessary to fully understand human substrate metabolism and the implications the presence of sexual dimorphism in the control of substrate kinetics has on the prevention and treatment of disease. J. Nutr. 135: 681-686, 2005.Within the past decade, a great deal of effort has been dedicated to uncovering the relevant physiologic differences between the sexes that may affect the prevention, diagnosis, and treatment of disease. For example, there are differences between the sexes in the lipid profile that may have clinical implications. In women, high plasma triglyceride (TG) 3 concentrations are independent and better predictors of cardiovascular disease risk than total or LDL cholesterol (1,2). Treatment of hypertriglyceridemia may, therefore, be of greater importance in women than in men. Also, differences in hepatic handling of fatty acids between men and women are likely responsible for the greater susceptibility of women to fatty liver disease and the more severe liver injury as a result of it (3). A better understanding of the control of lipid metabolism by a person's sex will therefore not only increase our knowledge of human intermediary and macronutrient metabolism, but may also be useful for the development of novel approaches for the treatment and prevention of disease.There are 2 general approaches when evaluating differences in metabolism between the sexes. One (clinically probably the most relevant) is to accept the differences in phenotype between men and women (e.g., body composition, regional fat distribution, aerobic fitness, all of which affect substrate metabolism in persons of the same sex) and acknowledge that the observed differences in lipid metabolism may be secondary to those characteristics. The other strives to eliminate as many potential confounding variables as practically feasible to determine whether sex per se represents an underlying factor in the control of metabolism.A simple view concerning the underlying cause for sexual dimorphism in metabolis...