Pancreatic cancer is still one of the most aggressive and fatal types of human cancer . Survival rates for patients with pancreatic cancer are extremely poor and one major contributing factor is the lack of specific marker(s) for the early detection of pancreatic cancer. Indeed, the great majority of pancreatic cancer cases are diagnosed at an advanced stage of the disease and these patients often have a poor response to treatment with conventional forms of therapy. In this article, we conduct a comprehensive review of the literature on the expression pattern, prognostic significance and predictive value of EGFR family members, IGF-IR and their ligands in pancreatic cancer. We also discuss recent advances in pancreatic cancer treatments and highlight the remaining challenges as well as future opportunities for more effective targeting of such receptors using a combination of growth factor receptor specific monoclonal antibodies, small molecule tyrosine kinase inhibitors and other therapeutic strategies. Such strategies could ultimately help to overcome the development of drug resistance and improve the overall survival rates for patients with pancreatic cancer.