Vanadium is a trace element, which may be beneficial and possibly essential in humans1 but certainly essential for some living organisms. 2r11 Metal ions and thus vanadium ions can play a role in biology as counterions for protein, DNA, RNA, and in various biological organelles. The structural role is often manifested by the maintenance of various biological structures, whereas a functional role is to bring key reactivity to a reaction center for a protein. Vanadium ions have many structural roles reflected by its structural and electronic analogy to phosphorus. 9, 12r20 In addition, the vanadium ion is an enzyme cofactor, 7, 9, 21r30 and is found in certain tunicates4r11, 16 and possibly mammals. 1 Reviews on how vanadium can act and function in the biosphere include investigations into the fundamental coordination and redox chemistry of the element, 16r18, 29, 31r35 as well as structural and functional aspects of biological systems and/or metabolites. 12, 36 Modeling biological activities of various types have long been of interest to chemists, with this discipline focusing on the structural modeling until about a decade ago when the focus shifted to functional modeling. Clearly modeling that includes both aspects will be most informative, and the ultimate goals for model chemists. Although the latter in general may be of greater interest at the present time, the structural aspects of the various oxidation states are defining its effects in many biological systems. In this review, we have combined the two fundamentally different aspects of modeling because the coverage of only one of these areas in our opinion would not provide the reader the proper sense of the effects and activities exerted by vanadium compounds (V-compounds). This review describes the voyage from the discovery of the first vanadium-containing enzymes in 1984, haloperoxidases, 7, 9, 21r26, 37, 38 to the current X-ray crystallographic studies; it is a fascinating story that provides inspiration to chemist in many fields. These studies map out the enzyme active site24, 39r43 and demonstrate the structural and functional link between apohaloperoxidases and certain phosphatases. 24, 39r43 These discoveries now give the bioinorganic chemists clear directives. The detailed mechanistic studies revealing how the enzyme-catalyzed reaction takes place, 7, 22, 23, 37, 38 to the design of simple vanadium complexes (V-complexes) exhibiting similar activities as the enzyme show how much the chemists can do. 7, 9, 29, 38, 44r48 Inhibition of phosphatases by V-compounds is firmly established, 9, 12r15, 19, 20 and often the versatility of the vanadium to bind as a four-coordinate ground state analogue and a fivecoordinate transition state analogue is not generally recognized; thus, V-compounds can act as substrates although bioinorganic chemists are more familiar with the five-coordinate transition state analogy as exemplified in the potent inhibition of phosphatases, ribonuclease, 49, 50 and other phosphorylases. Although