Radioiodinated metaiodobenzylguanidine (MIBG), or Iobenguane, was developed in the late 1970s at the Michigan University Medical Center for imaging the adrenal medulla and its diseases, and was rapidly extended to depict a wide range of tumors of neural crest origin. Because of its high and selective uptake and retention by these tumors, careful consideration was also given to the therapeutic potential of [(131)I]MIBG. Beside imaging and therapy of neuroendocrine tumors, the possibility of in vivo assessment of cardiac sympathetic neuronal activity led recently to a renewed interest for MIBG scintigraphy and this application is still expanding. In this paper, we review the evolution in the use of MIBG in more than 25 years of experimental and clinical applications, with attention also to the developments in radiochemistry and instrumentation. A literature search in PubMed based on ''metaiodobenzylguanidine or MIBG'' was conducted; from this analysis, it appears that the use of MIBG evolved from nearly exclusively oncology (both for diagnosis and therapy) to new applications mainly aimed to study the sympathetic neuronal integrity of the heart. Those currently exceed those about imaging of tumor diseases. We also report the geographic distribution of published papers.