Progress in the understanding of multiple myeloma (MM) cell biology has led to the identification of new relevant prognostic factors and subsequently different risk groups. This concept, together with the recent discovery of new drugs with novel mechanisms of action, will probably lead to individualized treatment according to the different patients' characteristics. In this review, we focus on current available agents already approved for MM, and discuss individualized treatment approaches for both transplantation candidates (subdivided into standard and high-risk patients) and elderly patients. Future progress in MM will be based on using science to inform the design of the optimal combined treatments, and high throughput assays that can assess the ability of combination therapies to induce death of MM cells, both alone and in the bone marrow microenvironment.