Neuroblastoma is the most common pediatric extracranial solid tumor. High-risk neuroblastoma is the most frequent presentation with an overall survival of approximately 50%. 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy in the assessment of the primary tumor and its metastases at diagnosis and after chemotherapy is a cornerstone imaging modality. In particular, the bulk of skeletal metastatic disease evaluated with 123I-mIBG at diagnosis and the following chemotherapy has a prognostic value. Currently, single-photon emission computerized tomography/computerised tomography (SPECT/CT) is considered a fundamental part of 123I-mIBG scintigraphy. 123I-mIBG SPECT/CT is a highly specific and sensitive imaging biomarker and it has been the basis of all existing neuroblastoma trials requiring molecular imaging. The introduction of SPECT/CT has shown not only the heterogeneity of the mIBG uptake within the primary tumor but also the presence of completely mIBG nonavid metastatic lesions with mIBG-avid primary neuroblastomas. It is currently possible to semi-quantitatively assess tracer uptake with standardized uptake value, which allows a more precise evaluation of the tracer avidity and can help monitor chemotherapy response. The patchy mIBG uptake has consequences from a theranostic perspective and may partly explain the failure of some neuroblastomas to respond to 131I-mIBG molecular radiotherapy. Various positron emission tomography tracers, targeting different aspects of neuroblastoma cell biology, are being tested as possible alternatives to 123I-mIBG.