The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as bortezomib, in the last decade have resulted in a new scenario expected to impact favorably on the outcome of MM patients. In the transplant and nontransplant setting, several randomized trials have shown that front-line treatment with bortezomib-based combinations are superior to conventional treatment and have allowed for a significant increase of complete response rate, with a positive impact on progression-free survival. Furthermore, this drug appears to be active in patients with high-risk disease and comorbidities. Thus, bortezomib-containing regimens are now considered as a new standard of care for newly diagnosed myeloma patients. In this article, we will attempt to overview the results of bortezomib when administered as a standard component of front-line therapy for MM patients.