High-dose melphalan therapy with peripheral blood stem cell (PBSC) transplantation is a standard treatment for younger patients with untreated multiple myeloma that results in high overall and complete response (CR) rates, and improved event-free and overall survival compared with standard chemotherapy alone. Induction therapy serves to reduce tumor burden prior to stem cell mobilization and thus must not adversely impact stem cell mobilization and harvesting, or engraftment following high dose therapy plus autologous stem cell transplantation. Bortezomib, an approved agent for the treatment of multiple myeloma patients who have received at least one prior therapy, is also being investigated in the frontline setting. Preclinical studies have demonstrated that bortezomib has no toxic effects on stem cells, megakaryocytes or neutrophil precursors, and causes only transient and reversible thrombocytopenia and neutropenia. Clinical studies with bortezomib-based induction regimens have demonstrated no adverse impact on PBSC harvest numbers nor on their quality as defined by engraftment times. These regimens appear to be well tolerated and highly active as induction therapy, with high response rates and consistently high CR rates. Randomized phase 3 studies comparing bortezomib-based regimens with current standard induction therapies are ongoing.