More than 30 years after its introduction, autologous stem cell transplantation (ASCT) remains the standard of care for young patients with newly diagnosed multiple myeloma. Not only did the arrival of novel agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and monoclonal antibodies not replace ASCT, instead they solidified its central role as standard of care. Novel agent use is now inarguably essential in induction, maintenance, and possibly consolidation. In light of these new advancements, new challenges arise in deciding on optimal practice. Who is most suited to undergo ASCT? Is there an age threshold that should not be surpassed? Should transplantation be embarked on early or is it reasonable to delay it? What are the optimal induction, consolidation, and maintenance therapies? What is the role of tandem transplantation in the era of novel agents and where do patient-specific cytogenetics come into the equation when deciding on treatment? These are some of the questions addressed in this review which we will attempt to answer with the latest currently available data.