The calpains are a family of calcium-dependent cysteine proteases that catalyze limited proteolysis of substrates. Calpain Inhibitor III is a cell permeable, selective inhibitor of μ-calpain (calpain-1) and m-calpain (calpain-2). Calpain Inhibitor III crosses the blood-brain barrier to inhibit brain cysteine protease activity and has been reported to have neuroprotective effects in numerous rodent neurotrauma models, including spinal cord injury, cortical impact trauma, neonatal hypoxia-ischemia, and focal cerebral ischemia. Additionally, Calpain Inhibitor III has been shown to attenuate depression in myocardial contractile performance that occurs during reperfusion following cardiac ischemia.