The extensive development of image fusion techniques over the past 20 y has shown that the fusion of images from complementary modalities offers a more complete and accurate assessment of disease than do images from a single modality. Although software techniques have been successful in fusing images of the brain from different modalities, they have achieved rather limited success for other parts of the body. The recent introduction of technology that can acquire both anatomic and functional images in a single scan has addressed many of the limitations of software fusion. The combination of CT and PET was introduced commercially in 2001, followed by CT and SPECT in 2004. Clinical adoption of PET/CT has been surprisingly rapid, and despite continuing debate, the new technology has advanced the use of clinical molecular imaging, particularly for oncology.