High dose chemotherapy has been used as consolidation in multiple myeloma by a number of investigators (Barlogie et al., 1986; Cunningham et al., 1994; Harousseau et al., 1995). A randomized trial conducted by French Myeloma Intergroup (IFM 90) provided evidence that treatment with high dose chemotherapy and autologous stem cell transplant (ASCT) after initial therapy results in significantly longer event-free survival (median 28 vs. 18 months) and overall survival (57 vs. 42 months) if compared to conventional chemotherapy (Attal et al., 1996). The benefit of auto transplantation was seen in patients of all ages (Siegel et al., 1999). More recently, similar results were reported from a large randomized study in Great Britain (Childs et al., 2003). Based on these studies, in patients eligible for transplant, consolidation of initial therapy with high dose therapy followed by ASCT is considered a standard of care (NCCN Guidelines 2004). However, ASCT is not curative even in patients who achieve complete response (CR), which is observed in 20-30% of patients who completed ASCT. Contamination of autologous stem cell collection with malignant myeloma cells may play some role. In support of this notion, syngeneic bone marrow transplants showed better and more durable outcomes than those seen with ASCT (Gahrton et al., 1999). Another reason for failure of autologous stem cell transplant is ineffective eradication of myeloma clone with high dose chemotherapy. In an effort to provide more effective elimination of malignant clones, some investigators developed intensified treatment regimens. Improved results have been reported using Total Therapy, which involves a sequence of treatments, including tandem ASCT (Barlogie et al., 1999, Barlogie at al., 2004). The notion that intensification of therapy improves outcomes has been validated in a recent randomized study, which showed that consolidation of initial therapy with tandem autologous stem cell transplant was superior than consolidation with single autologous stem cell transplant as measured by an improved duration of responses and overall survival (Attal at al, 2003). In contrast to ASCT, allogeneic stem cell transplantation can provide stem cell products free of malignant cells, as well as the benefit of graft-versus-myeloma effect.