The metabolic syndrome (syndrome X) is a cluster of risk factors and a common cause of cardiovascular disease in humans. Although the underlying mechanism for metabolic syndrome is still poorly understood, recent clinical data and studies with transgenic animals implicate elevated intracellular glucocorticoid tone in the etiology of metabolic syndrome. Development of selective inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-1 and their use in rodent animal disease models encompassing several aspects of metabolic syndrome indicate the possibility of therapeutic intervention. This review will focus on recent advances in our understanding of the role of 11beta-HSD1 in metabolic disorders and other disease processes.