Thal has antiangiogenic and immunomodulatory activity. Clinical research provided clear evidence that Thal belongs to the most active drugs for the treatment of multiple myeloma e.g. leading to decrease of monoclonal protein of at least 50 % in 30 % of patients with relapsed or refractory multiple myeloma. Randomized trials that were designed based on a large body of evidence from phase II trials determined that Thal significantly increases total response rate, progression-free and in some studies overall survival in combination regimens (dexamethason and or chemotherapy) for relapsed as well as newly diagnosed patients and was therefore approved for first-line treatment of Multiple Myeloma. Strict guidelines apply due to the teratogenic effects of Thal and to monitor and prevent other potential adverse events as neuropathy and thrombosis has been recognized by leading organizations as part of the treatment concept for patients with relapsed or refractory disease. The success of Thal has sparked the development of Thal analogues with Lenalidomide (Len) the most advanced compound which was approved for relapsed multiple myeloma. As Len has a lower incidence of polyneuropathy, constipation and somnolence compared to Thalidomid but at least equal if not higher efficacy Len is meanwhile used more frequently in clinical routine and has advantages in combination therapies with Bortezomib. Additional randomized studies will now define the status of Thal and Len for maintenance therapy and their optimal integration in multi-agent treatment regimen.