Thalidomide has been demonstrated to be active as a first-line and salvage therapy in patients with multiple myeloma. Numerous studies over the past 8 years have shown it to induce high response rates and improve event-free survival in newly diagnosed patients as well as those with relapsed/refractory disease. Recent randomized clinical trials have demonstrated that thalidomide-based regimens are superior to conventional treatments in terms of response rates and event-free survival. However, few trials have demonstrated a survival benefit with thalidomide, indicating the need for further trials. This review will focus on recent trials of thalidomide in relapsed/refractory and newly diagnosed multiple myeloma and address some of the common adverse events associated with thalidomide treatment.