Neuroendocrine neoplasms include two distinct entities with very different prognoses: neuroendocrine carcinomas (NECs, small and large cell) are often discovered at a metastatic stage and have a poor prognosis, whereas neuroendocrine tumors, which are well differentiated and rarely metastatic, show a slower evolution and much better prognosis. There has been little recent therapeutic progress in metastatic NECs, apart from the arrival of immunotherapy in addition to platinum and etoposide chemotherapy, achieving overall survivals of around 12 months. Meanwhile, a better understanding of the molecular profile of large cells could lead to a better adaptation of patient management, by preferring taxane- or gemcitabine-based chemotherapy in the case of an adenocarcinoma-like profile. Unfortunately, relapses in this situation are frequent, specific molecular alterations are rarely targetable, and immunotherapy is not effective enough to be administered alone. Neuroendocrine tumors have very different evolutions depending on the grade, the presence of secretory syndrome, and the tumor burden. For indolent disease, monitoring or the introduction of somatostatin analogues is recommended. In case of rapid evolution, refractory secretory syndrome, or high tumor burden, systemic treatment is required: everolimus-, temozolomide-, or oxaliplatin-based chemotherapy (FOLFOX, GEMOX) or peptide receptor radionuclide therapy if there is an expression of somatostatin receptors. In all cases, the therapeutic strategy must be discussed in an expert center because of the rarity of these diseases, and inclusion in clinical trials, when possible, must be preferred.