The frontline therapy for newly diagnosed multiple myeloma (MM) has continued to evolve over the last 10 years. There has been a growing emphasis on achieving the best depth of response in the context of minimal residual disease negativity, given its prognostic correlation with superior overall survival. Another important area of emphasis has been to improve prognostication and staging by including information on disease biology. There also a growing appreciation of global differences in drug access and patterns of care. The current review explores each of these areas and how best to incorporate the emerging induction regimens in to schema of MM therapy.