Multiple myeloma (MM) is an incurable malignancy of terminally differentiated B-cells accounting for approximately 1 to 2% of all human cancers. The development of MM is believed to be a multistep transformation process that leads to progressive accumulation of genetic alterations. The interaction between MM and bone marrow (BM) microenviroment triggers multiple proliferative and antiapoptotic signaling pathways. Here we discuss the current understanding of signaling pathways, and their potential implication in targeted therapies in MM.