During the last decade, positron emission tomography/computed tomography (PET/CT) and single-photon emission computed tomography/computed tomography (SPECT/CT) have procured advances in research and clinical application of fusion imaging. The recent introduction of digital PET/CT opens new horizons for multimodality molecular imaging. This system offers more precise, simultaneous morphologic, functional, and molecular information of a living system. Moreover, other combinations of anatomic and functional imaging modalities hold promise in basic medical research or in clinical medicine. These developments are paralleled by advances in the field of biomolecules and particles that will provide new agents useful for more than one imaging modality and will facilitate the study of the same target by different imaging devices. Digital PET/CT may emerge as a powerful multimodality technique with great clinical impact on the diagnosis and therapy assessment of oncological diseases due to its enhanced sensitivity.