Multimodality imaging is playing a key role in the clinical management of patients in routine diagnosis, staging, restaging and assessment of response to treatment, surgery and radiation therapy planning of malignant diseases. The complementarity between anatomical (CT and MRI) and functional/molecular (SPECT and PET) imaging modalities is now well recognized and the role of fusion imaging is widely used as a central piece of the general tree of clinical decision making. Moreover, dual-modality imaging technologies including SPECT/CT, PET/CT and nowadays PET/MR represent the leading component of a modern healthcare facility. There have been significant advances in data acquisition along with innovative approaches to image reconstruction and processing with the aim to improve image quality and diagnostic information. However, CT procedures involve relatively high doses to the patient, which triggered many initiatives to reduce the delivered dose particularly in paediatric practice.This chapter discusses the state-of-the-art developments and challenges of multimodality medical imaging technologies and dose reduction strategies. Future opportunities and the challenges limiting their adoption in clinical and research settings will also be addressed.