At the Myeloma 2015 meeting, Prof Kenneth Anderson (Harvard Medical School, Boston, MA) chairs a discussion with Prof Leif Bergsagel (Mayo Clinic, Scottsdale, AZ) and Prof Gareth Morgan (University of Arkansas, Fayetteville, AR) on studies involving potential new management options for multiple myeloma (MM). They focus on the clinical significance of tumor heterogeneity in MM, the utilization of genomics for improved classification of MM subtypes and the development of rationally based combination therapies for MM.