Abstract Multiple myeloma remains an incurable disease; however, newer biologically based therapies aimed at various molecular-cellular targets are showing promise. Some of these drugs target critical pathways of the tumor cell and the bone marrow microenvironment. A brief review of the pathogenesis of multiple myeloma is presented. Genetic aberrations are hallmarks of the disease. Chromosome 14 translocations are responsible for cellular processes implicated in tumorigenesis. Adhesion to the extracellular matrix and bone marrow stromal cells augments drug resistance and inhibits apoptosis. Bortezomib, a proteasome inhibitor, acts on bone marrow constituents blocking many signaling cascades mediating multiple myeloma cell growth, survival, and drug resistance. Bortezomib and other cell-cycle targeted therapies offer hope in the fight against multiple myeloma.