Multiple myeloma (MM) is the third most common hematologic malignancy in Korea. Historically, the incidence of MM in Korea has been lower than that in Western populations, although there is growing evidence that the incidence of MM in Asian populations, including Korea, is increasing rapidly. Despite advances in the management of MM, patients will ultimately relapse or become refractory to their current treatment, and alternative therapeutic options are required in the relapsed/refractory setting. In Korea, although lenalidomide/dexamethasone is indicated for the treatment of relapsed or refractory MM (RRMM) in patients who have received at least one prior therapy, lenalidomide is reimbursable specifically only in patients with RRMM who have failed bortezomib-based treatment. Based on evidence from pivotal multinational clinical trials as well as recent studies in Asia, including Korea, lenalidomide/dexamethasone is an effective treatment option for patients with RRMM, regardless of age or disease status. Adverse events associated with lenalidomide/dexamethasone, including hematologic toxicity, venous thromboembolism, fatigue, rash, infection, and muscle cramps, are largely predictable and preventable/manageable with appropriate patient monitoring and/or the use of standard supportive medication and dose adjustment/interruption. Lenalidomide/dexamethasone provides an optimal response when used at first relapse, and treatment should be continued long term until disease progression. With appropriate modification of the lenalidomide starting dose, lenalidomide/dexamethasone is effective in patients with renal impairment and/or cytopenia. This review presents updated evidence from the published clinical literature and provides recommendations from an expert panel of Korean physicians regarding the use of lenalidomide/dexamethasone in patients with RRMM.