Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare chromaffin cell tumors (PPGLs) that raise significant challenges in clinical recognition, diagnosis and therapy, and when under-diagnosed could associate with severe morbidity. Recent discoveries in PPGLs genetics improved our understanding in the pathophysiology of tumorigenesis and allowed the application of functional classification of pathogenetically distinct groups of PPGLs. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. For most of the cases, one or more molecular (functional) imaging methods are employed, such as 123I‑MIBG scintigraphy, 18F‑FDG or 18F‑DOPA PET/CT, or somatostatin receptor imaging. The selection of the functional modality could be based on knowledge of the patient's genetic background. The definitive treatment of PPGL is surgical excision of the tumor. However, in patients with progressive and widely metastatic PPGLs, the therapeutic options were limited until recent years to traditional chemotherapy using cyclophosphamide, vincristine, and dacarbazine (CVD), usually tolerated for long periods but with limited efficacy together with important side effects. Experience with other chemotherapeutic agents such as temozolomide is limited, whereas new data on several TKIs with mainly anti-angiogenic activity seem promising. Theranostics approaches using high-specific activity MIBG or peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin agonists are rapidly evolving in the setting of these tumors and are considered as a breakthrough in the therapeutic arsenal of metastatic PPGLs.