Osteoclasts are bone-resorbing cells derived from hematopoietic precursors of the monocyte-macrophage lineage. Besides the well known Receptor Activator of Nuclear factor-kappaB (RANK), RANK ligand and osteoprotegerin axis, a variety of factors tightly regulate osteoclast formation, adhesion, polarization, motility, resorbing activity and life span, maintaining bone resorption within physiological ranges. Receptor-mediated osteoclast regulation is rather complex. Nuclear receptors, cell surface receptors, integrin receptors and cell death receptors work together to control osteoclast activity and prevent both reduced or increased bone resorption. Here we will discuss the signal transduction pathways activated by the main osteoclast receptors, integrating their function and mechanisms of action.