Bone remodelling continues throughout life and depends on two processes that are tightly coupled: resorption of old bone by osteoclasts and subsequent new bone formation by osteoblasts. Evidence accumulated during the last few years has clearly indicated that bone marrow microenvironment plays an essential role in regulating bone remodelling. Indeed major advances in our understanding of the ontogeny of osteoclasts and osteoblasts indicate that both cell types derive from progenitors present in the marrow, and that systemic and local factors regulate their development and the coupling of their function. In particular, a network of cytokines and growth factors is essential for the regulation of both osteoclastogenesis and osteoblast formation: these factors play a pivotal role in the paracrine regulatory control of bone turnover under physiological conditions. Among this array of local factors, IL-6, IL-1, TNF, GM-CSF, cytokines with osteoclastogenic and bone resorptive properties, have been implicated in the pathophysiology of osteoporosis since their production is increased in vivo in humans and animals with estrogen deficiency. These findings provide emerging insights into the pathophysiology of osteoporosis and deserve further investigation.