Thalidomide is the first drug in over 20 years to demonstrate clinically significant activity in patients with multiple myeloma. Although the survival rate has not improved with conventional chemotherapy over the last 30 years, thalidomide has produced favorable responses in patients for whom most available therapies have failed, such as those whose disease was resistant or relapsed after standard and high-dose treatments. Despite the risk of adverse effects such as sedation and constipation, thalidomide has become an alternative therapy for patients with relapsed or refractory disease. New trials with thalidomide administered alone and in combination with other agents seem to show promise in patients with multiple myeloma, as do preliminary studies with thalidomide derivatives.