This chapter considers the potential of the Comet assay [or single-cell gel electrophoresis (SCGE)] for evaluating the environmental impact of genotoxins in aquatic environments. It focuses on in vivo and in situ studies that have been carried out using various marine and freshwater sentinel species. A large number of the studies reviewed report that the Comet assay is more sensitive when compared with other biomarkers commonly used in genetic ecotoxicology, such as sister chromatid exchanges or the micronucleus test. The Comet assay is widely influenced by laboratory procedures, suggesting that standard protocols are required for both vertebrate and invertebrate species and tissues. However, there is still a wide variety of differing Comet procedures evident in the literature reviewed, making comparison between published results often very difficult. Standardization and inter-laboratory calibration of the Comet assay as applied to aquatic species will be required if the Comet assay is to be used routinely by national bodies charged with monitoring water quality.