Upgrading wastewater treatment plants (WWTPs) with advanced technologies is one key strategy to reduce micropollutant emissions. Given the complex chemical composition of wastewater, toxicity removal is an integral parameter to assess the performance of WWTPs. Thus, the goal of this systematic review is to evaluate how effectively ozonation and activated carbon remove in vitro and in vivo toxicity. Out of 2464 publications, we extracted 46 relevant studies conducted at 22 pilot or full-scale WWTPs. We performed a quantitative and qualitative evaluation of in vitro (100 assays) and in vivo data (20 species), respectively. Data is more abundant on ozonation (573 data points) than on an activated carbon treatment (162 data points), and certain in vitro end points (especially estrogenicity) and in vivo models (e.g., daphnids) dominate. The literature shows that while a conventional treatment effectively reduces toxicity, residual effects in the effluents may represent a risk to the receiving ecosystem on the basis of effect-based trigger values. In general, an upgrade to ozonation or activated carbon treatment will significantly increase toxicity removal with similar performance. Nevertheless, ozonation generates toxic transformation products that can be removed by a post-treatment. By assessing the growing body of effect-based studies, we identify sensitive and underrepresented end points and species and provide guidance for future research.