Increasingly, upregulation of antiapoptotic proteins have been implicated in the pathogenesis and in the development of chemotherapy resistance in multiple myeloma. Therapeutic interventions that target the apoptotic pathway in myeloma are attractive targets to treat resistant disease. Dexamethasone triggers apoptosis via the release of Smac (second mitochondria-derived activator of caspase) leading to the activation of caspase-9 and caspase-3.37 The proteasome inhibitor bortezomib blocks signal transduction pathways mediated by NF-κB including the regulation of antiapoptotic genes such as TRAF1 and 2 (TNF receptor-associated factors) and cIAP (cellular inhibitor of apoptosis) and BCLXL.