High-dose chemotherapy with autologous hematopoietic stem cell reconstitution is efficacious in the treatment of multiple myeloma. The various preparative regimens, sources of hematopoietic stem cells, and post-transplant immunomodulation are discussed. Tandem autotransplantation following intravenous melphalan chemotherapy has low morbidity and mortality even in patients with refractory disease. The most encouraging results are observed in patients undergoing high-dose chemotherapy with less prior treatment, lower tumor mass, and sensitive disease.