The matrix metalloproteinases (MMPs) and their tissue-specific inhibitors (TIMPs) are described and their roles in tumor invasion and metastasis are reviewed. The expression and activity of the MMPs and TIMPs in pancreatic cancer is reported and illustrated with immunohistochemistry and in situ hybridization. The role of MMP inhibitors (MMPIs) is reviewed in vivo and the use of novel MMPIs, e.g., BB94 (Batimastat) and BB2516 (Marimastat); in animal experiments are also described. Finally, the preliminary results from a phase 2 trial of BB2516 (Marimastat) in pancreatic cancer are reported.