The treatment of multiple myeloma (MM) has changed dramatically in the past twenty years with the introduction of high-dose therapy plus autologous stem-cell transplantation (ASCT) in younger patients and, more recently, of three novel agents (thalidomide, bortezomib, and lenalidomide). When conventional chemotherapy was the only available possibility, complete responses (CR) were very rare and the objective of maintenance was to prolong remission duration by continuing the same type of treatment that induced the initial response. With recent therapeutic improvements, CR achievement becomes a realistic goal that, in most cases, is significantly correlated with the outcome (1). Therefore, both the nature and the impact of maintenance therapy have changed. Maintenance therapy is based currently on novel agents, and its objective is not only to control the clone but also to further decrease the tumor burden and improve the quality of response. A number of randomized studies show a benefit from maintenance therapy with novel agents (until now, mostly thalidomide), at least in terms of response rate and progression-free survival (PFS). However, there is still a debate as concerns the impact on overall survival (OS) and the optimal administration of maintenance therapy.