Growing evidence suggests that extracellular nucleotides, signalling through P2 receptors, might play important roles in the regulation of bone and cartilage metabolism. ATP and other nucleotides can exert impressive stimulatory effects on the formation and activity of osteoclasts (bone-resorbing cells) in addition to inhibiting bone formation by osteoblasts. In this review, the current understanding of the actions of nucleotides on skeletal cells and the probable receptor subtypes involved are discussed.