The unique ability of the osteoclast to degrade skeletal tissue depends upon formation of a resorptive microenvironment between the osteoclast and the bone surface. Generation of this privileged space is substantially mediated by signals emanating from αvβ3 integrin, which transits to its active high-affinity conformation by growth factor-initiated intracellular events targeting the matrix receptor's cytoplasmic domain. The activated liganded integrin stimulates a signaling complex consisting of c-Src, Syk, immunoreceptor tyrosine-based activation motif proteins, Slp-76, Vav3, and members of the Rho family of GTPases. These events contribute to secretory lysososme insertion into the bone-apposed plasma membrane to form the ruffled border that delivers the bone-degrading molecules (HCl and cathepsin K) into the resorptive microenvironment. Integrin/bone recognition also promotes formation of actin rings, which surround the ruffled border, thereby isolating the focus of skeletal degradation from the general extracellular space.