Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value in the disease. Based on the increased angiogenesis observed in myeloma, thalidomide (Thalomid) has been studied as antiangiogenic therapy. Although its mechanism of action in myeloma is unclear, several trials show that thalidomide is active in 25% to 35% of patients with relapsed myeloma. Since many patients who respond have failed other active regimens, including transplantation, these results are impressive. Major toxicities include constipation, sedation, skin rash, fatigue, and peripheral neuropathy. Studies are ongoing to determine its role as initial treatment for myeloma. Trials are also underway combining thalidomide with other active agents. This article summarizes the current status of thalidomide therapy in myeloma.