Although multiple myeloma remains an incurable disease, its management has changed recently with the introduction of novel agents, including bortezomib. Several pilot studies and two randomized trials have evaluated the role of bortezomib-based combinations as induction therapy in myeloma patients who are candidates for transplant, showing high efficacy (>80% response rate with 20-30% complete remission), which increased after autologous stem cell transplant. In addition, in patients who are not candidates for transplant, bortezomib in combination with melphalan and prednisone has also been found to be superior to conventional therapy, with high overall and complete response rates; responses were rapid and durable and there was a significant prolongation in time to progression and overall survival. Moreover, bortezomib has broad utility since its efficacy is not influenced by the presence of poor prognostic features, such as high-risk cytogenetic abnormalities, renal impairment or advanced age. These results allow bortezomib-based combination therapy to be established as key options for patients with previously untreated multiple myeloma.