During the last decades, radiation oncology has undergone transformative technological advancements including the clinical implementation of ion beam therapy, most commonly using protons and carbon ions and more recently also helium ions as a high-precision treatment modality. Due to its distinct physical and biological advantages, which lead to superior dose distribution with a steep dose-fall-off at the distal end of the irradiation field, ion beam therapy benefits particularly from image guidance. Especially, molecular imaging can provide functionally related insights not only for target volume delineation, but also into tumour subpopulations, and enables individualized treatment adaptation, such as dose escalation and de-escalation or a local boost in regions where higher doses are required. This article provides an overview of clinical molecular imaging with positron emission tomography (PET) with particular relevance in ion beam therapy. As in-vivo beam range verification is of particular interest in ion beam therapy and also related to PET, this article covers this topic as well.