Most metastatic pheochromocytomas and paragangliomas (mPPGLs) require systemic therapy, and targeted radionuclide therapy is an efficient option in this setting. Low-specific-activity and high-specific-activity formulations of 131I-meta-iodobenzylguanidine (131I-MIBG) are historically the most commonly used radiopharmaceuticals for targeted radionuclide therapy in mPPGL and both of them have demonstrated their value in this scenario, with a relevant response rate in a considerable number of patients. Hematological toxicity may be experienced with these therapies as well as catecholamine release syndrome and other adverse effects. Peptide receptor radionuclide therapy (PRRT) is the second type of radionuclide treatment available for mPPGLs, and it is performed with labeled DOTA compounds (177Lu-DOTATATE, 90Y-DOTATOC, and 90Y-DOTATATE). The experience with PRRT is more limited compared to MIBG, but different studies have demonstrated its role in mPPGLs. For this treatment, the kidneys and bone marrow are the dose-limiting organs and there is a risk of catecholamine release syndrome, together with other adverse effects. Comparisons between 131I-MIBG therapy and PRRT have been proposed, but the available data are not sufficient to support the advantage of one treatment over the other or to support sequential or combined therapies.