The bony biochemical environment is an active and dynamic system that permits and promotes cellular functions that lead to matrix production and ossification. Each component is capable of conveying important regulatory cues to nearby cells, thus effecting gene expression and changes at the cytostructural level. Here, we review the various signaling molecules that contribute to the active and dynamic nature of the biochemical system. These components include hormones, cytokines, and growth factors. We describe their role in regulating bone metabolism. Certain growth factors (i.e., TGF-beta, IGF-1, and VEGF) are described in greater detail because of their potential importance in developing successful tissue-engineering strategies.