The global Earth ecosystem faces many intertwined threats, primarily anthropogenic pollution, drastic reduction of wild spaces, faster spread of pathogens, and global climate warming. Ecotoxicology, the integration of toxicology and ecology, aims to describe the effects of toxicants on organisms, whether at the level of the population, the community, the ecosystem, or the biosphere. Sentinel species are employed to assess threats to life, giving advance warning of danger. In this issue of Proteomics, Wilde and collaborators (Proteomics 2022, 22) present a comprehensive coverage of the proteome of the crustacean Daphnia magna, a species used to evaluate aquatic pollution. This study illustrates how current shotgun proteomics technology allows straightforward quantitation of any protein for whole animals or dissected organs, making global molecular phenotyping a reality for animals. Tandem mass spectrometry operated in data-independent acquisition can be used to compare the response of sentinels to various environmental conditions. The current low number of well-annotated animal or plant genomes, the high diversity of genetic backgrounds of each species, and the paucity of knowledge about protein functions for most of the relevant sentinels pose huge challenges for data interpretation. As a result, ecology and ecotoxicology today constitute an exceptional field for proteomics!