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The present editorial introduces to a Special Issue in Environmental Science and Pollution Research journal, highlighting selected papers presented at the 19th International Symposium on Toxicity Assessment (ISTA19) that was held in Thessaloniki, Greece, in August 2019. For more than 30 years, the biennial ISTA congresses serve as a catalyst for fruitful exchanges between researchers, managers, and legislators involved in all fields of environmental science, safety, and health. ISTA provides a forum for discussions on current advances in toxicity and risk assessment, on fundamental or innovative concepts in ecotoxicology, as well as on research on environmental protection and conservation. Nowadays, investigation of environmental toxicity is more necessary than ever; the general public is continuously bombarded with various environmental agents—some of them less than innocuous, permissible exposure limits for workers are commonly revaluated and new scientific data enable us to ban, limit, restrict, or re-register pesticides and other chemicals. At the same time, novel testing technologies and tools continue to emerge. These techniques utilize fewer live organisms and they are in vitro and in silico oriented. Thus, there is a need for developing a long-range vision and strategy for toxicity testing that encompasses more humane methods without compromising validity and reliability. Only this approach will be able to give answers to current and imminent environmental problems. The following 12 manuscripts are just a glimpse of these concerns that were talked about in ISTA19. At the same time, these selected manuscripts demonstrate the breadth of toxicity assessments being conducted globally. It would be a great disservice to ISTA’s ideology if we forgot where we originated from; as such, the special issue opens with the participation of Professor Paule Vasseur and her team (Vasseur et al. 2020) on how it all started with “Ecotoxicology, revisiting its pioneers.” Right after diving into the past, we emerge in the present with the presentation of an ultrarapid screening test developed by Snell and Persoone (2020). The test uses a desiccated rotifer which, when rehydrated, can easily classify water-based samples into four toxic categories. From novel bioassays to well-established ones, we continue with the research of Courtois et al. (2020) on how the model organism Eisenia foetida accumulates and biotransforms Ag, which is increasingly used in agriculture, especially in nanoparticle form. Staying in the crop field, we then investigated the hrpZPsphtransgenic Nicotiana benthamiana response under Cd stress (Mitsopoulou et al. 2020) and how it differs from its wild-type homologue. The realistic threat of Cd soil contamination as well as Cr contamination was the focus of research of Antoniadis and Golia (2020) on agricultural soils in Central Greece. It was shown that the pollution arises from fertilizers, but it also has a lithogenic component. Contamination of soil by toxic metals was also the research focus of the review of Charvalas et al. (2021). Case studies of Chalikidiki and Kozani in Greece were chosen in order to showcase the potential of phytoremediation, in relation to the local flora characteristics. Intensive agriculture and clashing land uses further facilitate soil metal contamination in Greece; as such, our own research here (Giannakis et al. 2020) examined how land Responsible editor: Philippe Garrigues