The discovery that multiple myeloma is associated with new vessel formation and is correlated with survival and proliferation led initially to the use of thalidomide for patients with relapsed or refractory disease. The outcome with conventional chemotherapy in this setting has historically been very poor. New insights into the biology of the disease suggests that thalidomide may work via a number of other mechanisms and the advent of the thalidomide analogues with their differential effects on survival and proliferation pathways has opened up a new era in the understanding and treatment of the disease. The encouraging results from phase I/II trials of these agents has meant that for the first time in 50 years there is the opportunity to improve outcome. Further work is in progress to define how best to use these drugs and their role in treatment at different stages of the disease.