Objective. In this article we focus on the role that chemokines and chemokine receptors play in the pathogenesis of multiple myeloma and the associated bone destructive process, and consider their utility as novel therapeutic targets for treating this devastating disease. Methods. Current research on the role that chemokine and chemokine receptors play in the pathogenesis of myeloma is reviewed. Results. The chemokines, MIP-1 alpha, MCP-1, IL-8, and SDF-1, and their receptors play important roles in homing of MM cells, tumor growth, and bone destruction in myeloma. They are attractive therapeutic targets for treating myeloma patients. Conclusion. Addition of chemokine antagonists to current treatment regimens for myeloma should result in better therapeutic responses because of the loss of both the protective effect of the marrow microenvironment on the MM cells and the induction of osteoclast activity. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.