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The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177. In this review, covering twenty five years of literature, we describe the characteristics and performances of the two most used therapeutic radiopharmaceuticals for the NETs radio-treatment: [⁹⁰Y]Y-DOTATOC and [¹⁷⁷Lu]Lu-DOTATOC taking this opportunity to retrace the most significant results that have determined their success, promoting them from preclinical studies to application in humans.