Skeletal development and bone remodeling depend on the coordinated activity of osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively. Mature osteoclasts result from the fusion of precursor cells, and they are large, multinucleated, highly specialized cells. Cellular release of ATP and UTP occurs in response to a variety of stimuli including mechanical stimulation, which occurs in the bone environment. ATP and UTP or their metabolites can then act on P2 receptors in the plasma membrane to induce various responses in bone cells. The influence of these receptors on osteoclast physiology and bone physiology in general is beginning to be understood, but much work is still required. This review focuses on P2 receptors in osteoclasts, their expression, signaling and function in the regulation of osteoclast formation, resorptive activity and survival.