Thalidomide and the analogues lenalidomide (CC-5013, Revlimid®) and CC-4047 (Actimid®) belong to the family of immunomodulatory drugs (IMiDs). These agents have anti-angiogenic properties, modulate TNFα and IL-12 secretion, co-stimulate T cells, increase NK cell toxicity and have direct anti-tumour effects. These characteristics have made of them promising drugs for treatment of relapsed, refractory and newly diagnosed MM. It seems that lenalidomide and CC-4047 are more powerful in inhibiting TNFα and have, except for myelosuppression, less side effects than Thal. Combination of IMiDs with dexamethasone, bortezomib and with chemotherapeutic agents are tested in numerous trials, which will help in determining the optimal combination and administration schedule of different molecules to take advantage of non-overlapping toxicities and synergisms between those agents.