Lenalidomide is a novel immunomodulatory agent with a unique dual mechanism of action: its tumoricidal effect leads to direct tumor cell death, and its immunomodulatory effect keeps the tumor in remission. Phase III clinical trials have demonstrated that in patients with relapsed/ refractory multiple myeloma (MM), lenalidomide in combination with dexamethasone offers high clinical response rates and improved time to disease progression, progression-free survival (PFS), and overall survival (OS) compared with dexamethasone alone. In patients with newly diagnosed MM, the combination of lenalidomide and low-dose dexamethasone prolonged survival compared with lenalidomide and standard high-dose dexamethasone. The benefits of lenalidomide-based treatment regimens can be optimized by initiating treatment early in the disease course, either as a frontline treatment or at first relapse. Lenalidomide is generally well tolerated; the primary adverse events are myelosuppression and venous thromboembolic complications. These adverse events emerge early in the course of treatment and can be managed using standard interventions such as granulocyte colony-stimulating factor, dose reduction, and thromboprophylaxis. The combination of lenalidomide and dexamethasone is effective and generally well tolerated in patients with renal impairment provided that creatinine clearance level and adverse events are carefully monitored and the starting dose of lenalidomide is adjusted appropriately. Early results from phase III trials indicate that in patients with newly diagnosed MM, continuous lenalidomide therapy is well tolerated and associated with significant improvements in PFS, offering a new treatment option for patients with MM -although no OS benefit has yet been seen in this setting. Lenalidomidebased treatment is effective across the spectrum of MM disease phases, allowing for the long-term management of myeloma.