Pancreatic cancer is the most lethal abdominal malignancy due to its aggressive growth and rapid development of distant metastases, thus making treatment extremely difficult. Additionally, pancreatic adenocarcinoma is locally invasive, surrounded by a dense desmoplastic reaction which can involve adjacent vital structures, limiting the number of patients who are candidates for surgical resection at the time of diagnosis. Recently the tumor microenvironment in other adenocarcinomas has been determined to be an important mediator of cancer cell behavior; however, few studies have elucidated the tumor-stroma interactions in pancreatic cancer. This review summarizes the role of pancreatic stellate cells, perineural invasion, angiogenesis, and inflammatory cells in fostering pancreatic cancer cell growth and invasion. The importance of extracellular matrix proteins, growth factors, and cytokines is also presented. Finally we suggest ideas for new avenues of research into the pancreatic tumor microenvironment which may permit the development of novel, more effective treatments for pancreatic cancer.