Although endocrine tumors are diverse and heterogeneous, some express specific receptors or are able to internalize selected peptides, ions, or amine, making them prime targets for nuclear therapy. Indeed, neuroendocrine tumors, differentiated thyroid cancers, and pheochromocytomas/paragangliomas express respectively somatostatin receptors, the Na+/I− symporter, and the monoamine transporter. Among therapeutic options, radionuclide therapies specific of these targets are efficacious and well-tolerated treatments. However, the current radionuclide therapies use beta-particles, which are nonoptimal with a long penetration range in the tissue and a low linear energy transfer (LET). In contrast, alpha-particles have a much higher LET and a very short range in the tissue that can induce a greater number of ionizations and DNA double-strain breaks while minimizing damage to healthy tissue. Preclinical studies showed the advantages of alpha-particle therapy in endocrine tumors, and clinical studies in neuroendocrine tumors demonstrated the efficacy of alpha-particles in patients refractory or unsuitable to beta-therapy. This chapter summarizes the current preclinical and clinical investigations concerning alpha-particle therapy in endocrine tumors.