Pancreatic cancer is characterized by multiple genetic abnormalities that can be used as targets for specific therapeutics. The HER family consists of four transmembrane growth factor receptors. Targeting HER1 with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib demonstrated a survival advantage for patients with advanced pancreatic cancer. Multiple other agents that target members of the HER family are under investigation. These include reversible and irreversible, single and pan HER tyrosine kinase inhibitors. Chimeric, humanized and fully human monoclonal antibodies that target specific HER receptors are also being studied. These agents are also radiation sensitizers. This article reviews clinical trials of HER family inhibitors in pancreatic cancer, discusses the role of these agents in the management of patients and outlines future directions for pancreatic cancer management.