Patients with metastatic gastrointestinal neuroendocrine tumors have traditionally been faced with few effective treatment options. Somatostatin analogs often successfully control symptoms of hormonal hypersecretion but seldom result in tumor regression. Some patients with hepatic metastases are also candidates for ablative therapies such as surgical debulking or embolization. The role of systemic agents such as interferon alfa or cytotoxic chemotherapy remains ill defined. The more prevalent use of these modalities has been restricted by low tumor response rates and the potential for toxicity. Novel agents, including radiolabeled somatostatin analogs, inhibitors of the vascular endothelial growth factor pathway, and inhibitors of mammalian target of rapamycin, have shown promising activity in recent clinical studies. Continued investigation of these agents should render a better understanding of their efficacy in patients with advanced neuroendocrine tumors.