Multiple myeloma is a multi-step disease, and different steps have different sensitivities to chemotherapy and radiotherapy.Low sensitivity can result in recurrent and refractory multiple myeloma.The growth of myeloma cells, apoptosis inhibition and drug resistance depend on the participation of immunomodulatory cytokines and vascular endothelial growth factors, such as IL-6 and VEGF.Thalidomide, an effective drug for multiple myeloma, has both anti-angiogenesis effect and immunoregulatory function; but long term use of thalidomide can result in complications such as deep venous thrombosis.Immunomodulatory drugs (IMiDs)are more effective thalidomide analogues and they have become a focus of study.IMiDs have anti-angiogenesis effect; they can co-stimulate T cell subgroup, induce cytokine production, and increase the quality and quantity of NK cells, exerting cytotoxic effect against tumor cells via antibody dependent manner.This article reviews the mechanism of IMiDs in treatment of multiple myeloma and the preliminary result of the clinical trails.