The chemokine CXCL12 (variously termed stromal-derived factor 1 or B cell-stimulating factor) is a highly conserved chemotactic cytokine belonging to the large family of CXC chemokines. CXCL12 has crucial roles in the formation of multiple organ systems during embryogenesis and in the regulation of bone marrow haematopoiesis and immune function in the postnatal organism. Although considered an important factor in normal bone metabolism, recent studies implicate CXCL12 in the pathogenesis of several diseases involving the skeleton, including rheumatoid arthritis and cancers that metastasize to bone. Recent studies have highlighted an emerging role for CXCL12 in the processes of physiological and pathological bone remodelling.