Lenalidomide is an immunomodulatory drug derived from thalidomide, developed to maximize its anti-inflammatory and antineoplastic properties while reducing toxicity. Lenalidomide administered orally at 25 mg/d on days 1-21 of 28-day cycles plus dexamethasone is indicated for the treatment of relapsed/refractory multiple myeloma patients, who received at least one prior therapy. In the pivotal MM-009 and MM-010 Phase III registration trials, lenalidomide-dexamethasone, when compared with placebo-dexamethasone, significantly improved response rate (60 vs 20%, respectively), time-to-progression and survival. The most common adverse events included hematologic toxicity and venous thromboembolism. The drug is currently being investigated for the treatment of newly diagnosed myeloma and, in association with chemotherapy drugs (cyclophosphamide and melphalan) or novel agents (bortezomib, carfilzomib and elotuzumab), for the development of highly active combination regimens.