The cells of the osteoblast lineage (osteoblasts, osteocytes, and bone lining cells) have multiple stage-specific functions in the skeleton, including formation of the bone matrix. They arise from pluripotent mesenchymal progenitors, which can also give rise to adipocytes and chondrocytes. The functions carried out by the osteoblast lineage are regulated by both paracrine and endocrine factors. During bone formation, osteoblasts produce the collagenous matrix (osteoid), which becomes mineralized through the deposition and accumulation of bioapatite mineral crystals; the latter is dependent on the availability of inorganic phosphate, which is regulated by the osteoblast lineage through production of alkaline phosphatase, and other non-collagenous proteins. During osteoid deposition, osteoblasts can become embedded within their own matrix, and differentiate further, to become interconnected osteocytes. Alternatively, they may remain on the surface as bone lining cells, which have the potential to become reactivated into matrix-producing osteoblasts. The osteoblast lineage also supports osteoclast formation and thereby regulates bone resorption through the production of receptor activator of NF-ΚB ligand (RANKL), colony-stimulating factor 1 (CSF-1), and osteoprotegerin (OPG), a decoy receptor for RANKL. This versatile cell lineage therefore not only forms bone but can also controls its removal, which makes understanding the stage-specific roles of the osteoblast lineage crucial for targeting many skeletal conditions, such as osteoporosis, osteogenesis imperfecta, and other pathological conditions.