Maintenance therapy was recently defined as any treatment administered after the completion of induction therapy in patients whose disease is either responsive or nonprogressive at the time, with the goal of prolonging survival. Several studies have evaluated the use of novel agents as part of posttransplantation maintenance to improve progression free survival and overall survival. As shown by recent clinical trials, thalidomide and bortezomib are more indicated as consolidation agents, increasing the response rates. In contrast, lenalidomide showed a low toxicity profile and a benefit from prolonged treatment, making the drug one of the best choices for maintenance treatment. The role of lenalidomide in the maintenance therapy was evaluated in three randomized clinical trials. Lenalidomide was associated with a significantly increased progression free survival and in one study with a significant survival benefit. An unexpected finding from these trials was a modest increase in the incidence of secondary cancers. Whether lenalidomide maintenance should be routinely off ered to patients is controversial among experts. For now, lenalidomide maintenance should be considered standard for patients not achieving a complete remission after stem cell transplantation, and for high-risk patients. For patients with low- risk disease, the risk/ benefits of lenalidomide maintenance versus watchful waiting should be discussed until we have more data regarding survival benefits. Further analysis of lenalidomide maintenance therapy to determine the long-term risk of secondary malignancies and longer follow-up to assess the impact on overall survival is required.