Melphalan-prednisone (MP) was introduced for the treatment of MM in late 1960s. In the subsequent 30 years, the treatment improvements remained stagnant, since more complex chemotherapy combinations, such as vincristine, doxorubicin, and dexamethasone (VAD), or with the addition of BCNU (VBAD) or melphalan and cyclophosphamide (VCMP), only led to small increases in the overall response rate but without differences in survival, as assessed in a large meta-analysis that included over 6000 patients. The next step forward was the use of high-dose melphalan followed by stem cell support (autologous stem cell transplant - ASCT) for young myeloma patients, which resulted in a significant improvement in disease free survival and overall survival. However, for elderly patients MP remained as the standard of care. From year 2000, a revolution in the treatment armamentarium of MM has emerged with the availability of new agents with singular mechanism of action such as thalidomide and lenalidomide (Revlimid®), both immunomodulatory drugs and the proteasome inhibitor bortezomib (Velcade®).