Evasion of apoptosis (programmed cell death) is a hallmark of pancreatic cancer, one of the leading causes of cancer deaths in the western world. Resistance to apoptosis can promote the multistep process of tumorigenesis, since tissue homeostasis is disturbed by too little cell death. Further, defects in apoptosis programs can leads to treatment failure in pancreatic cancer, since intact apoptosis pathways are critical to mediate therapy-induced cytotoxicity. Over the last decade, the exploration of apoptosis pathways and their dysregulation in pancreatic cancer has resulted in the identification of molecular targets that can be exploited for drug development and clinical application. Such apoptosis-based cancer therapeutics open new perspectives for rationally designed treatment strategies for patients with pancreatic cancer.