Ecotoxicological risk assessment has long been based on (acute) effective concentration and lethal concentration (EC/LC50) endpoints in organisms from different trophic levels. These tests are insufficient adequately to assess the risk associated with many chemical classes. The introduction of advanced molecular techniques is leading to improved risk assessment and is also providing an alternative to the massive use of animal testing. Transcriptional profiling and DNA chips are highly informative and are among the most promising novel techniques for environmental risk assessment. Moreover, information discerned from these chips enables the identification of new discriminative biomarker genes. Based on these biomarker genes, cellular reporters can be constructed. These can be used in a high-throughput set-up and can facilitate ecotoxicological risk assessment significantly. Some important technical and interpretative hurdles still need to be overcome before a full implementation of ecotoxicogenomics in regulatory settings will occur.