Bone development and the adaptation of the adult skeleton to mechanical needs and hormonal changes depend on the ability of bone cells to resorb and form bone in the right places and at the right time. Bone growth, modeling, or remodeling is defined by the spatial and temporal relationship between bone resorption and bone formation. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes detect the need for bone augmentation or reduction and coordinate the activities of osteoclasts and osteoblasts. Osteoclasts are the primary bone resorptive cells and originate from precursors of the hematopoietic lineage on stimulation with the RANK ligand (tumor necrosis factor ligand superfamily member 11/receptor activator of the NF-κB ligand) and macrophage colony-stimulating factor 1. The rate of osteoclast generation determines the extension of the basic multicellular unit, whereas the life span of osteoclasts determines the depth of resorption. Osteoblasts are the cells responsible for bone formation and originate from mesenchymal progenitors that also give rise to chondrocytes, muscle cells, and adipocytes. Osteocytes are former osteoblasts that remain within the mineralized bone matrix and form a network that senses mechanical and hormonal environmental cues and orchestrates the function of osteoblasts and osteoclasts. This chapter discusses the current knowledge on the generation, fate, and function of bone cells.