Treatment of patients with multiple myeloma has shown considerable progress these last two decades. While autologous stem cell transplantation seems to be agreed as the "gold standard" of front-line treatment in the young patients, the result of IFM99-06 prospective study would probably lead to a change regarding treatment of elderly as patients who received the thalidomide-melphalan-prednison association had better overall survival than those who received either the standard melphalan-prednison association or an intensive treatment. The best innovative therapeutic concept is illustrated by the new molecules that target both the myeloma cells and the bone marrow microenvironment. Thus, thalidomide and derivatives (Revlimid and the Actimid) and Velcade have transformed considerably the history of multiple myeloma. They have not to be considered as competitors but rather complementary whose impact will probably come of their combination and their association with the intensive treatments. The issues of maintenance therapy and allogeneic stem cell transplantation in the treatment of patients with myeloma remain to be addressed.