Radioiodinated metaiodobenzylguanidine (MIBG) was developed in the late 1970's, at the Michigan University Medical Center, for imaging of the adrenal medulla and its diseases. Soon after, MIBG was shown to depict a wide range of tumors of neural crest origin other than pheochromocytomas/paragangliomas (Pheo/PGL) with the result that its use rapidly spread to many countries. After more than 30 years of clinical application, MIBG continues to be the most widespread radiopharmaceutical for the functional imaging of Pheo/PGL in spite of the emergent role of PET agents for detection of these tumors. In this paper we review the evolution in the use of MIBG over more than 30 years of experimental and clinical applications, with particular focus on the uptake mechanisms, pharmacokinetics, biodistribution and drug interaction as well as on clinical studies in Pheo/PGL also in comparison to other gamma-emitters tracers and PET radiopharmaceuticals.