Bone lesions are a prominent feature accompanying multiple myeloma. Elucidation of the mechanisms regulating osteolysis is crucial in achieving a good quality of life, as such patients suffer from bone pain even after achieving improvement of the disease by high-dose chemotherapy. Recent research has revealed that bone lysis in myeloma patients is the result of both inhibited bone formation and enhanced bone destruction. It has been considered that bone absorption is regulated by activation of osteoclasts mediated by osteoclast activating factor (OAF) produced from myeloma cells. Macrophage inflammatory protein-1 alpha (MIP-1a) is a member of the chemokine family, and was originally determined as a soluble factor secreted from activated macrophages. Many candidates for OAF had been proposed and MIP-1a is now considered a major OAF. In this review, the significance of MIP-1a in myeloma bone disease is summarized.