During the course of disease multiple myeloma subclones acquire more and more additional genetic changes causing an aggressive proliferative growth with less responsiveness to therapeutic agents. On the other hand new therapeutic options are getting available, leading to the question, if a more intensive treatment in newly diagnosed myeloma patients may result in a better outcome concerning progression-free survival, quality of life and overall survival. In newly diagnosed myeloma patients, physicians have to distinguish between patients eligible for autologous stem cell transplantion (ASCT) and patients ineligible for ASCT. Transplant eligibility is mainly based on biological age, performance status and co-morbidities. New data suggest that prolonged treatment—synonymously called maintenance therapy—may lead to additional survival benefit even in the elderly/frail patient group. Yet there is no clear data on overall survival for prolonged treatment. At time the first-line armoury in myeloma consists of chemotherapy, steroids, proteasome inhibitors and immunmodulatory/antiangiogenetic drugs. The role of new antibodies in myeloma treatment is evolving but there is only limited (but promising) data available yet. New agents might reduce the therapeutic side-effects of an intensive treatment despite increasing efficacy as shown, e.g., for the new proteasome inhibitor carfilzomib. In the first-line setting, other new oral proteasome inhibitors with low dose-limiting neurotoxicity rates will be available shortly. In this short review, therapeutic strategies will be discussed focusing on treatment intensity.