The sequencing of many vertebrate species over the last decade has opened up the possibility of using comparative genomics as a powerful tool to elucidate regulatory elements in the vertebrate genome. The zebrafish has played a pivotal role in this process. Its genome has been used in large-scale genome comparisons to locate vertebrate specific regulatory elements and also it has been an excellent model system to test out the predicted DNA sequences for their ability to drive reporter gene expression in vivo. In spite of all the successes there have still been some issues in using the zebrafish as a model system for these kinds of assays. This review will shed some light on the successes and failures of the zebrafish in pushing forward regulatory genomics.