Multimodality image registration and fusion have a key role in routine diagnosis, staging, restaging, and the assessment of response to treatment, surgery, and radiotherapy planning of malignant disease. The complementarity between anatomic (CT and MR imaging) and molecular (SPECT and PET) imaging modalities is well established and the role of fusion imaging widely recognized as a central piece of the general tree of clinical decision making. Moreover, dual modality imaging technologies including SPECT/CT, PET/CT, and, in the future, PET/MR imaging, now represent the leading component of contemporary health care institutions. This article discusses recent advances in clinical multimodality imaging, the role of correlative fusion imaging in a clinical setting, and future opportunities and challenges facing the adoption of multimodality imaging.