Bone formation and resorption are normal physiologic processes. In pathologic states such as in periodontal disease or osteoporosis a shift in the balance of these two processes occurs, resulting in a net loss of mineralized tissue. Osteoclasts have historically been considered to be the primary bone resorbing cells, but current research has lead to the hypothesis that osteoblastic cells play an integral role in bone resorption as well. It appears that osteoblasts respond to bone resorbing agents via a series of intracellular responses after interactions with specific surface receptors. Two basic pathways involving different "second messengers" have been identified. The first pathway involves cyclic 3',5' adenosine monophosphate (cAMP) production and the second involves membrane phospholipids, diacylglycerol and calcium. A cytosolic enzyme, protein kinase C (PKC), has been shown to affect both cAMP as well as calcium fluxes and may act to regulate both these pathways. It is the purpose of this paper to discuss current studies and hypotheses concerning the nature of mechanisms involved in regulation of bone metabolism with emphasis on second messenger systems. Information of this nature is critical to the development of rationale regarding diagnosis, treatment and management of systemic and local pathoses of bone.