Vanadium is a trace element present in practically all cells in plants and animals. It exerts interesting actions in living systems. At pharmacological doses, vanadium compounds display relevant biological actions such as mimicking insulin and growth factors as well as having osteogenic activity. Some vanadium compounds also show antitumoral properties. The importance of vanadium in bone arises from the studies developed to establish the essentiality of this element in animals and humans. Bone tissue, where the element seems to play an important role, accumulates great amounts of vanadium. This paper reviews the physiology of osteoblasts, the involvement of different growth factors on bone development, and the effects of vanadium derivatives on the skeletal system of animal models and bone-related cells. Two cellular lines are discussed in particular; one derived from a rat osteosarcoma (UMR106) and the other is a nontransformed osteoblast cell line (MC3T3-E1). The effects of different growth factors and their mechanisms of action in these cellular lines are reviewed. These models of osteoblasts are especially useful in understanding the intracellular signaling pathways of vanadium derivatives in hard tissues. Vanadium uses an intricate interplay of intracellular mechanisms to exert different biochemical and pharmacological actions. The effects of vanadium derivatives on some cellular signaling pathways related to insulin are compiled in this review. The comprehension of these intracellular signaling pathways may facilitate the design of vanadium compounds with promising therapeutic applications as well as the understanding of secondary side effects derived from the use of vanadium as a therapeutic agent.