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.