AbstractThere has been great progress in the design of vectors for cancer gene therapy. However, it has been difficult to translate success in the laboratory into clinical practice. A major hurdle in understanding these failures has been the relative difficulty in monitoring repeatedly and non‐invasively the biodistribution, gene expression and replication of these viral vector systems. With the advent of molecular imaging technology, this deficiency is being rapidly rectified. A number of reporter genes have been used to monitor gene expression. In this review, we discuss the role of the sodium iodide symporter (NIS) as a reporter and therapeutic gene for cancer gene therapy when combined with various radioactive isotopes. © 2003 Wiley‐Liss, Inc.