Toxic metals remain a current important threat to aquatic ecosystems, despite regulatory efforts to reduce their release. Several toxic metals already appear in the list of priority substances polluting surface waters, while concerns arise from the increasing use of technology-critical metals such as metallic nanoparticles, rare-earth, and platinum group metals. In aquatic environments, various chemical, biological and physical processes determine the impact of metals on the biota. This review provides insights into responses to toxic metals recently reported in freshwater and marine animals. The specific emphasis is on: (i) common cellular and molecular responses; (ii) stress proteins; (iii) redox homeostasis; (iv) cytoskeleton rearrangement; (v) metabolism reshuffle; (vi) free cellular energy and mitochondrial metabolism; and (vi) immunity. These endpoints are promising, notably in multi-biomarker approaches to identify precise cellular toxicity pathways and anticipate the impact of environmental metal pollution.