Multiple Myeloma (MM) remains an incurable plasma cell malignancy in the bone 
marrow (BM) despite conventional therapies as well as high-dose therapies with 
stem cell support. Therefore novel biologically-based therapeutic approaches are 
required. Recently, intensive laboratory and preclinical studies have identified 
and validated therapeutic molecular targets in MM. In particular, recognition of 
the biologic significance of the BM microenvironment in MM pathogenesis and as a 
potential target for novel therapeutics has derived several promising 
approaches. Novel FDA approved agents including thalidomide/thalomid, its 
immunomodulatory derivatives lenalidomide/Revlimid, and proteasome inhibitor 
bortezomib/Velcade are directed at molecular targets not only in MM cells but 
also in its BM milieu, and have already achieved promising results in clinical 
studies. Here we discuss the mechanisms of action of these novel drugs and their 
clinical application, alone or combined with conventional or novel drugs.