Pancreatic ductal adenocarcinoma (PDA) and severe acute pancreatitis (AP) are still unresolved problems in routine clinicalpractice. Although the biologies of these diseases are fundamentally different, both forms share the problem of high morbidity, mortality and lack of specific therapeutic options. Therapy in these diseases is mostly symptomatic or non-specific. Over the last few years a huge body of evidence has emerged supporting a fundamental role of the IKK/NF-kB/Rel signalling pathway in the pathophysiology of pancreatic ductal adenocarcinoma and acute pancreatitis. The therapeutic potential and benefit of targeting NF-κB in pancreatic disorders and the possible complications and pitfalls of such an approach, are explored in this review.