The sodium iodide symporter gene (NIS) is expressed abundantly in the thyroid gland where its role is to concentrate iodine from the bloodstream into cells against a concentration gradient. This iodine is then used for the synthesis of thyroxine by the thyroid. NIS cannot distinguish between normal and radioactive iodide, and this has long been exploited for diagnosis and treatment of certain thyroid diseases. When the NIS gene is expressed artificially in non-thyroid cells, whole body radioiodine imaging (using PET or SPECT) can be used to pinpoint their location, and therapeutic doses of radioiodine can be administered to mediate their destruction. Conveniently, radioactive pertechnetate can substutute for radioiodine in these imaging studies. The NIS technology can be used to monitor the performance of vectors used for gene therapy applications, to determine the fate of cells administered for regenerative medicine applications and even to increase the antitumor potency of oncolytic viruses. For example, we have generated genetically modifed oncolytic measles viruses, and vesicular stomatitis viruses to express NIS and have shown that the intratumoral spread of these viruses can be noninvasively monitored by serial SPECT-CT imaging studies in mice and, more recently, in human patients enrolled in virotherapy clinical phase I trials. For cell fate determination, human mesenchymal stem cells were transduced by NIS-expressing lentiviral vectors and imaged in vivo in research animals using a microSPECT-CT machine. Currently, we estimate that about 10e6 NIS expressing MSC can be seen reliably in the mice when deposited subcutaneously. Unlike luciferase imaging, the NIS technology can be applied not just in small animals but also in larger animals and human subjects because it relies on radioisotopic imaging. Also, unlike luciferase or HSV thymidine kinase, the NIS protein is nonimmunogenic. For future studies, we hope to increase the resolution of detection by improving levels of NIS expression and using other vector systems to deliver the NIS gene into cells of interest.