High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has been used in the treatment of multiple myeloma since the early 1980s. Its present position as the backbone of first-line treatment in patients up to 60 to 65 years of age is the result of several controlled randomized trials, where its superiority over standard chemotherapy has been demonstrated. However, the method is not considered to have curative potential, with the possible exception of a small proportion of about 5% to 10% of patients with very long-standing complete remissions (CRs) of more than 8 years. Over the years, there have been several attempts to improve the technique, where, for example, tandem transplants and post-transplant maintenance treatment have been successful, at least in certain subgroups of patients, while others, such as graft purging, have been of no value. Treatment results need further improvement, particularly in poor-prognosis disease--based on abnormal karyotype and high beta2-microglobulin--and the future will show if the introduction of novel drugs like bortezomib, thalidomide, and lenalidomide will lead to longer survival and prolongation of disease control in multiple myeloma.