An editorial notes that various effective induction regimens are now available for the treatment of multiple myeloma in older patients who are ineligible for stem-cell transplantation, but two-drug regimens such as lenalidomide and dexamethasone remain an important option for patients deemed to be too frail to receive more intense therapy. Therefore, selection of an appropriate regimen will become a more challenging and complex process that is based on the unique clinical characteristics of a given patient.