Methods for treating multiple myeloma with inhibitors of CXCR4, such as AMD3100 and anti-CXCR4 antibodies, are described. The decreased expression of CXCR4 on multiple myeloma cells according to the invention results in decreased homing of the cells to the bone marrow and a reduction in the development of the disease. Also disclosed are pharmaceutical compositions incorporating such inhibitors for use in the therapeutic treatment of multiple myeloma. The treatment methods described herein can be used independently, or in conjunction with, other therapies for the treatment of multiple myeloma.