Over the last decade, high-dose therapy supported by autologous stem cell transplantation (ASCT) has been the standard frontline therapy for younger patients with multiple myeloma (MM). But recently, the treatment strategy has been dramatically changed after the introduction of novel agents such as thalidomide, bortezomib and lenalidomide. These agents have been incorporated into induction therapies before ASCT and into consolidation and maintenance after ASCT, resulting in improvements in the complete remission (CR) rate with the prolongation of progression-free (PFS) and overall survival (OS). Now the best available strategy to achieve high CR rate and prolong PFS seems induction with three-drug bortezomib-based combinations followed by ASCT with bortezomib or immunomodulatory drugs-based consolidation, and lenalidomide maintenance. However, the best timing of ASCT in the era of novel agents represents an area of active debate and major interest. Currently several new agents are being developed, and more effective induction regimens using these agents with ASCT will upgrade responses and prolong PFS and OS in the near future.