Multiple myeloma (MM) accounts for about 1.8% of all cancers and slightly over 17% of hematologic malignancies. Despite improvements in outcomes in recent years, currently, there is still no cure for this disease. Although allogeneic stem cell transplantation (Allo-SCT) is a potentially curative treatment, given the armamentarium of highly effective therapeutic options and a pipeline of novel agents, many opinion leaders sustain that there is no longer a role for this approach. Of note, several studies that did not include novel agents reported long-term molecular remissions, and possibly a cure, in a subset of patients after reduced-intensity conditioning/nonmyeloablative (RIC/NM) Allo-SCT. However, there are no current data supporting upfront Allo-SCT. Prospective trials combining the so-called "graft-versus-myeloma" effect and new drugs are an unmet medical need in high-risk patients. Early relapse after first-line treatment, which identifies patients with poor prognosis independently of other prognostic factors, could become a clinical indication.