It is evident that various types of tumor cells use different mechanisms to inhibit apoptosis. Recent increased understanding of the many factors involved in the apoptotic process has identified potential targets for the restoration of the apoptotic response in pancreatic tumor cells. The ultimate goal is to develop effective therapeutic strategies to control this devastating disease. The aim of this chapter is to review signaling pathways involved in apoptosis by providing an account of the signaling molecules involved. This chapter reviews the literature on traditional apoptotic signaling pathways with special emphasis on pancreatic cancer. Involvement of G-protein coupled receptors and inositol phosphates in pancreatic apoptosis is also reviewed. Finally we have reviewed the literature on nutritional impacts on pancreatic apoptosis as an example of an environmental risk factor for pancreatic cancer. Knowledge about diverse effects on signaling molecules may serve as a basis for pancreatic cancer chemotherapeutic applications focused on apoptotic mechanisms.