Molecular medicine enhances the clinician's ability to accurately diagnose and treat disease, and many technological advances in diverse fields have made the translation of molecular medicine to the clinic possible. Nuclear medicine encompasses 2 technologies--single-photon emission computed tomography (SPECT) and positron emission tomography (PET)--that have driven the field of molecular medicine forward. SPECT and PET, inherently molecular imaging techniques, have been at the forefront of molecular medicine for several decades. These modalities exploit the radioactive decay of nuclides with specific decay properties that make them useful for in vivo imaging. As recently as the mid-1990s, SPECT and PET were mostly restricted to use in the clinical setting because their relatively coarse spatial resolution limited their usefulness in studying animal (especially rodent) models of human disease. About a decade ago, several groups began making significant strides in improving resolution to the point that small-animal SPECT and PET as a molecular imaging technique was useful in the study of rodent disease models. The advances in these 2 techniques progressed as the result of improvements in instrumentation and data reconstruction software. Here, we review the impact of small-animal imaging and, specifically, nuclear medicine imaging techniques on the understanding of the biological basis of disease and the expectation that these advances will be translated to clinical medicine.