The role of the proteasome in carcinogenesis and cell survival has been well established, and its inhibition associated with an accumulation of pro-apoptotic proteins and cell death. Proteasome inhibitors, such has bortezomib, have been extensively studied and are widely used as effective therapy in the treatment for hematologic malignancies, such as multiple myeloma where circulating proteasome levels have been correlated with survival. Carfilzomib, a novel irreversible proteasome inhibitor which specifically targets the chymotryptic site of the proteasome has shown more potency than bortezomib and may be able to overcome bortezomib resistance. Response rates between 25-54% were seen in patients with previously treated myeloma in the phase 2 setting.