The treatment of patients with multiple myeloma has changed in the last decades, with an improved median survival of 8-10 years. The current treatment for newly diagnosed multiple myeloma patients eligible for autologous transplantation consists of 4 phases: pretransplant, induction, transplant, post-transplant consolidation and maintenance. Even today, a long-term disease control is the goal of multiple myeloma treatment in current clinical practice. In this review we discuss the role of autologous stem cell transplantation in multiple myeloma, the eligibility of patients for transplantation and the usefulness of an upfront tandem transplantation. The assessment of frailty and significant comorbidities plays an important role in determining transplant eligibility. Careful patient selection based on overall health status is crucial to ensure a balance between risks and benefits. In the era of induction regimens with new agents, upfront autologous transplantation remains the standard of care for young patients with newly diagnosed multiple myeloma due to the longer progression-free survival showed in randomized clinical studies. With the currently available data, the tandem transplantation in multiple myeloma may be considered in patients with high-risk cytogenetics, in particular, those who did not receive a new triplet combination or those with a lower response than very good partial response following their first transplantation.