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We review different uses of the retroviral mutagenesis technology as the tool to manipulate the zebrafish genome. In addition to serving as a mutagen in a phenotype-driven forward mutagenesis screen as it was originally adapted for, retroviral insertional mutagenesis can also be exploited in reverse genetic approaches, delivering enhancer- and gene-trap vectors for the purpose of examining gene expression patterns and mutagenesis, making sensitized mutants amenable for chemical and genetic modifier screens, and producing gain-of-function mutations by epigenetically overexpressing the retroviral-inserted genes. From a technology point of view, we also summarize the recent advances in the high-throughput cloning of retroviral integration sites, a pivotal step toward identifying mutations. Lastly, we point to some potential directions that retroviral mutagenesis might take from the lessons of studying other model organisms.