Abstract: Hypersecretion of catecholamines from pheochromocytoma and paraganglioma(PPGL) is associated with high morbidity and mortality, even when the tumors are benign. Up to 25% of PPGL are associated with germline mutations in susceptible genes. About one-quarter is metastatic, defined by the presence of distant metastases. Treatment options for unresectable metastatic disease, including chemotherapy, ¹³¹I-MIBG, and radiation, can offer limited tumor and hormone control, although none are curative. Over the past 10 years, substantial progress has been made toward understanding the clinical aspects and molecular origins of PPGL. Nevertheless, predicting and managing malignancy remains the biggest challenge in clinical practice. The natural history of patients with metastatic PPGL has not yet been described, and their prognosis varies. Currently, the diagnosis of metastatic PPGL relies on the presence of metastases, and by then, the disease is usually advanced. A better understanding of the clinical and molecular characteristics of patients with metastatic PPGL has spurred several prospective clinical trials. A deeper understanding of the alteration of the specific molecular pathways causing metastatic PPGL might hopefully lead in the future to the development of radiotherapy and multiple molecular-targeted therapies to treat it successfully.