Early in the history of nuclear medicine imaging it was realized that the nature of physiological mechanisms associated with the use of radiotracers prevented the identification of anatomic structures with a high degree of accuracy. This limitation often created difficulties in accurate interpretations of acquired images and caused investigators to seek methods of obtaining accurate anatomic correlations. Initial work centered on the use of software tools to combine anatomic and physiological data. Limitations in the use of these techniques, coupled with the development and refinements of anatomic imaging technologies (computed tomography [CT] and magnetic resonance imaging [MRI]), resulted in the development of hybrid imaging systems that combined CT with single-photon emission computed tomography (SPECT) and positron emission tomography (PET). With these hybrid systems, the images can be viewed separately or combined in a fused presentation for direct image correlation of anatomy and physiology. Presently, SPECT systems are available either with nondiagnostic CT capability for attenuation correction and image correlation, or with fully diagnostic CT capability, providing complementary diagnostic information. Equivalently, PET systems with diagnostic CT capability that provide high-resolution physiological and anatomic images are also now commercially available. These systems continue to evolve with the development of new detector materials and data acquisition and image processing technology. The widespread use of SPECT in cardiac imaging has resulted in the development of several new approaches to data acquisition and these new systems currently have either CT capability or the addition of this technology is planned in the future. The development and commercial availability of hybrid imaging systems has provided physicians with important new tools that significantly improve the diagnostic, staging, and treatment planning processes that are now available for their use.