The current therapeutic strategy for multiple myeloma has improved dramatically due to the use of novel agents. In newly diagnosed transplant-ineligible myeloma patients, the standard therapy until the 1990s had long been melphalan and prednisolone (MP), but the recent recommendation is the proteasome inhibitor bortezomib plus MP (MPB), the immunomodulatory drug thalidomide plus MP (MPT), and the thalidomide derivative lenalidomide (LEN)-based regimens such as LEN plus low-dose dexamethasone (Ld) and LEN plus MP (MPL). The overall response rate in patients treated with Ld, MPL, or MPB was reported to be approximately 70%. Achieving complete remission (CR) is important in elderly as well as younger patients. Therefore, MPB administration appears to be the most appropriate initial therapy because the MPB regimen results in high CR rates. However, in elderly patients, especially in those 75 years of age and older and those who are frail or with comorbidities, it is important to balance efficacy and toxicity as well as to maintain quality of life. Furthermore, continuous treatment results in longer survival than a fixed-duration regimen in this population.