The ubiquitin-proteasome pathway plays a central role in the degradation of 
proteins involved in several pathways including the cell cycle, cellular 
proliferation and apoptosis. Bortezomib is the first proteasome inhibitor to 
enter clinical use, and received approval by the Food and Drug Administration 
(FDA) for the treatment of patients with multiple myeloma, therefore validating 
inhibition of the proteasome as an anticancer target. The approval of Bortezomib 
was based on a large, international, multicenter phase III trial showing its 
efficacy and safety compared with conventional therapy. Preclinical data also 
demonstrates the synergistic effect of bortezomib with other chemotherapeutic 
agents and its ability to overcome drug resistance. Since then several other 
proteasome inhibitors have been developed. The anti-tumor activities of 
bortezomib have been attributed to its effect on pro-apoptotic pathways 
including the inhibition of NF-kappaB and induction of endoplasmic reticulum 
stress. However, the molecular mechanisms are not fully understood. In this 
review, we will summarize the molecular mechanism of apoptosis by bortezomib.