Despite intensive therapy, multiple myeloma (MM) remains an incurable disease, and novel treatment approaches are therefore needed to improve outcome. Bortezomib is the first proteasome inhibitor to be approved by the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products for the treatment of refractory or relapsed MM following the failure of at least two prior lines of therapy. Recently, it also received approval from the FDA for use as a second-line agent. An expert panel of hematologists met at the Ninth Congress of the European Hematology Association to review clinical data and experience in the treatment of MM with bortezomib, including bortezomib-based combination therapy. The conclusions of this expert panel, together with updated clinical data from the American Society of Hematology 46th Annual Meeting, provide a practical update on the use of bortezomib in MM. Bortezomib has demonstrated significant antitumor activity as a single agent in refractory and/or relapsed MM, with a significantly longer survival than with dexamethasone (1-year overall survival rate of 80% vs. 66%) and a 78% longer median time to progression. In combination therapy, patient responses suggest the possibility of chemosensitization and synergy. Furthermore, bortezomib does not appear to have an adverse effect on subsequent stem cell therapy. Bortezomib is well tolerated; most side effects are only mild to moderate and are manageable. Information is given on the practical management of the most common adverse events, including peripheral neuropathy and thrombocytopenia, and the use of bortezomib in renal and hepatic impairment.