There is an ongoing increase in global population which is coupled with the excessive use of various resources from the human population. This significantly exacerbated environmental challenges and impacts and especially increased detection of pollutants in surface waters. While various analytical techniques are employed in water monitoring to identify contaminants, the analytical methods employed are often inadequate to provide early predictions and fail to capture the underlying mechanisms for observed effects in the ecosystem. This limitation highlights the need for more comprehensive approaches to pollution assessment. Consequently, there is a growing support for effect-based methods used to assess responses from key species, such as daphnids and others to pollutants. Daphnids are sentinel species often employed as indicators for the ecosystem. In the context of New Approach Methodologies (NAMs), these provide significant advantages in toxicity responses with extrapolations to more complex organisms. Our research focused on the impact of pharmaceuticals which are commonly encountered pollutants, on the physiology of daphnids. The integration of phenotypic endpoints such as feeding with key enzyme activities and metabolic perturbations points to the discovery of mechanisms in the actions of pharmaceuticals which serve as metrics for their detection in the environment, thus aiming to elevate the water flea as an equivalent to “a canary in the coal mine” to identify the presence of pharmaceuticals in the environment in actual river samples.