The subject of this chapter is The protease of Vibrio cholerae (PrtV). The PrtV peptidase is a secreted, Asp-zincin metallo-endopeptidase best characterized from the bacterium Vibrio cholerae, the causative agent of cholera. PrtV degrades host fibronectin, fibrinogen, and plasminogen. PrtV is stabilized at low temperatures by binding Ca2+. PrtV protects the bacterium from predation, killing Caenorhabditis elegans, by allowing the bacterium to colonize the nematode intestine. PrtV also processes the bacterial cytolysin VCC, modulating its exotoxin activity including lysis of erythrocytes and intestinal epithelial cells.