Neuroendocrine tumors (NETs) are a group of tumors originating in various locations, including the gastrointestinal tract, lung, and pancreas. Clinical trial design and disease management of these tumors pose a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The recent completion of several phase II and III trials demonstrates that rigorous investigation of novel agents can lead to practice-changing outcomes. Furthermore, the molecular and genetic understanding of NETs has dramatically improved during the last few years; as a result, investigators have shifted clinical trial design to focus on targeted therapies. Most of these trials have targeted the somatostatin, vascular endothelial growth factor, and mammalian target of rapamycin pathways. This review will discuss the NET treatment landscape and trials of targeted agents currently offered.