Tumor angiogenesis is a critical factor in the growth and metastasis of most malignant neoplasms. Thalidomide (Thalomid), banned from clinical use in the 1960s because of severe teratogenicity, has been shown to possess antiangiogenic properties. A recent clinical trial of antiangiogenic therapy with thalidomide demonstrated significant activity in a group of patients with relapsed refractory myeloma. Although its mechanism of action remains unclear, several trials have since confirmed that thalidomide is active in 25% to 35% of patients with relapsed myeloma. As a result, thalidomide has reemerged in clinical practice and is now actively being studied in the treatment of several cancers. Major toxicities associated with the use of thalidomide include constipation, sedation, skin rash, fatigue, and peripheral neuropathy. This article summarizes the current status of thalidomide therapy in cancer.