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The imaging of molecular events in the complex physiological interplay between organelles, cells, tissues, and organs in the whole organism is now more practical through the use of small-animal imaging technologies. Radionuclide based molecular imaging using single photon emission computed tomography (SPECT) and positron emission tomography (PET) scanners have been used for imaging intracellular enzymes, receptors, transporters, reporter gene expression, and cell trafficking in small animals such as mice and rats. Sensitive cooled charge-coupled device (CCD) cameras which detect emitted light from fluorescent and bioluminescent probes within an organism have been useful in imaging pathologic changes in diseases such as cancer and infectious disease in small-animal models. Each molecular imaging modality has differing strengths and weaknesses. However, the ability to generate molecular reporter strategies that can be applied in multiple detection systems will likely provide more robust imaging data sets than from any single modality. The ultimate function of multimodality reporter strategies will be to provide information about molecular targets in a continuum of research subjects from cells to small animals to human patients.