Vanadium is a trace element which is essential for certain organisms such as ascidians, polychaete worms and Amanita mushrooms. However, there is only limited information about its essentiality for mammals and humans. In this chapter, the current understanding of the mechanisms of uptake of vanadium in the gastrointestinal tract, release into the blood, biotransformation in the plasma and transport and complexation within the cell are described. In the blood and cells, interconversion between the most relevant oxidation states (+IV and +V) and binding with the most important proteins and low-molar-mass ligands of the biological fluids play a key role and affect the biochemical action. The mechanism of cellular uptake depends on the properties of the particular vanadium species involved. In the absence of exhaustive data about transport across biological membranes, recent studies have explored the way in which vanadium compounds associate with interfaces of membrane model systems. The analogy between phosphate and vanadate(V) is related to the inhibition and stimulation of several cellular enzymes and proteins and can explain most of the pharmacological effects. Vanadium metabolism is also discussed. Finally, the uptake, accumulation and binding of vanadium in ascidians and polychaete worms, in the mushroom Amanita and in bacteria are discussed briefly.