The introduction of proteasome inhibitor and immunomodulatory drugs has considerably changed the treatment paradigm of multiple myeloma. Autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy and is considered the standard of care for patients younger than 65 years. Nevertheless, the favorable results shown by multidrug inductions, consolidations, and long-term maintenance approaches have challenged the role of ASCT. This article provides an overview of recent and ongoing clinical trials and aims to define the role of ASCT in the era of novel agents.