Cytogenetic testing is now routinely performed for the prognostic work-up of multiple myeloma (MM). The abnormalities del(17p), t(4;14) and del(13q) have been established as predictors of poor outcome in patients with MM treated with conventional chemotherapy or stem cell transplant; chromosome 1q gains and 1p losses have also been identified as novel prognostic factors. In recent years, bortezomib and lenalidomide have emerged as effective treatments for both relapsed/refractory and newly diagnosed MM. However, the effect of cytogenetic abnormalities is unclear among patients with MM treated with these novel agents. Here we review recent studies that analyze the impact of specific genomic aberrations on the outcome of MM treated with bortezomib and/or lenalidomide.