The majority of patients will respond to initial chemotherapy, however, all treated patients repeatedly relapse with shorter remissions following each subsequent course of chemotherapy (Rajkumar et al., 2002a). Regimens most commonly used for initial therapy include melphalan and prednisone (MP), which induce remission in approximately 50% of patients (Alexanian et al., 1969), VAD—vincristine, adriamycin and dexamethasone with response rates in the 50% range (Salmon et al., 1994; Barlogie et al., 1984; Alexanian et al., 1986), dexamethasone pulses, and more recently introduced combinations of thalidomide with dexamethasone (Rajkumar et al., 2002b; Weber et al., 2003). All these regimens have comparable response rates. With the exception of the recent report, which showed a superior response rate to the combination of thalidomide with dexamethasone versus dexamethasone pulses (Rajkumar et al., 2004), multiple other comparative studies did not show superiority of any of these regimens for overall survival. Complete responses to any of these regimens are observed infrequently (< 5%). Patients who complete initial therapy, usually proceed to high dose chemotherapy with autologous stem cell transplant support. Alternatively, patients may be placed on maintenance regimen or can be observed. Except for one study with alternate day high dose of Prednisone (Berenson et al., 2002), no convincing evidence exists that maintenance impacts the natural history of the disease (Kyle, 2002; The Myeloma Trialists' Collaborative Group, 2001).