Multiple myeloma (MM) is a B cell malignancy that accounts for 10% of all hematologic cancers. In recent years much has been learned regarding the biology of the myeloma clone; specifically on the chromosomal alterations that can be more frequently found and on the involved oncogenes. It has been also demonstrated that, in MM, bone marrow microenvironment, both in its cellular (stromal cells, osteoblasts, osteoclasts, endothelia) and protein (extracellular matrix) components, plays an important role in promoting growth and survival of malignant plasma cells. Much of this knowledge will be translated into a better patients treatment; although high-dose therapy programs can be considered the treatment of choice for patients aged 70 or younger, novel drugs, targeting MM clone in its microenvironment can be incorporated into these therapeutic programs improving response rate and patients survival.