At the Myeloma 2015 meeting, Dr Keith Stewart (Mayo Clinic, Scottsdale, AZ) chairs a discussion with Prof Gareth Morgan (University of Arkansas, Fayetteville, AR) and Prof Leif Bergsagel (Mayo Clinic, Scottsdale, AZ) on studies involving new strategies for treating multiple myeloma (MM) that are guided by new insights in the disease biology. They focus on immune modulators and inhibitors of critical signaling pathways in MM.