The bone tissue‐specific osteocalcin gene remains one of a few genes that exhibits osteoblast‐restricted expression. Over the last decade, characterization of the promoter regulatory elements and complexes of factors that control suppression of the osteocalcin gene in osteoprogenitor cells and transactivation in mature osteoblasts has revealed transcriptional regulatory mechanisms that mediate development of the osteoblast phenotype. In this review, we have focused on emerging concepts related to molecular mechanisms supporting osteoblast growth and differentiation based on the discoveries that the osteocalcin gene is regulated by homeodomain factors, AP‐1 related proteins, and the bone restricted Cbfa1/AML3 transcription factor. J. Cell. Biochem. Suppls. 30/31:62–72, 1998. © 1998 Wiley‐Liss, Inc.