When diagnosed at an early stage, resection of pancreatic neuroendocrine tumors (NETs) is often curative. Unfortunately, curative surgery is rarely an option for patients with metastatic disease. Multiple options are available for the management of patients with advanced pancreatic NETs, including surgery, liver-directed therapy, and systemic therapies. Because of the heterogeneity of disease biology and presentation, a multidisciplinary approach to management is critical. Treatment with somatostatin analogs, sunitinib, everolimus, and alkylating agents provide effective systemic therapeutic options for patients. Future studies to evaluate the optimal timing, sequence, and combination of therapies, as well as to identify predictors of response, are warranted.