11Beta-hydroxylation is essential for glucocorticoid and mineralocorticoid activity of a steroid. The enzyme catalyzing this reaction is termed 11beta-hydroxysteroid-dehydrogenase (11beta-HSD). Two isoenzymes of 11beta-HSD have been characterized in human tissues. Whereas 11beta-HSD-I works mainly as a reductase, 11beta-HSD-II only functions as an oxidizing (inactivating) enzyme for physiological glucocorticoids. Thus, the tissue distribution of both enzymes plays a crucial role for the specific glucocorticoid status of an organ. This review summarizes our knowledge of tissue distribution of both 11beta-HSD isoenzymes, their physiological function and pathophysiological role in certain clinical abnormalities, and their relevance to the metabolism of synthetic glucocorticoid and mineralocorticoid compounds.