Natural Populations are increasingly challenged by rapidly changing environmental conditions. Toxic compounds produced from industrial and urban activities present a significant challenge to aquatic organisms. Heavy metals, in particular, are common stressors that play a major role in environmental damage. Since aquatic systems are the major sinks of industrial effluents they are often more highly impacted by heavy metals than terrestrial ecosystems. Understanding the fitness consequences of heavy metal exposure requires knowledge of the physiological responses of organisms and the genetic basis of these responses. This information is critical to environmental scientists interested in predicting the long-term consequences of altered environments, and to regulatory agencies constructing predictive models to assess the impact of pollutants on human and environmental health.We evaluate the underlying genetic architecture and transcriptional responses of the freshwater microcrustacean Daphnia magna to cadmium exposure in order to identify genes and pathways involved in the physiological response to this common environmental contaminant. We use QTL-mapping in recombinant lines derived from parental lines that differ in their response to cadmium exposure to detect genome regions associated with survivorship, and cadmium assimilation and depuration rates. In addition, we use a functional genomic approach with RNA-Seq data to examine transcriptional responses to cadmium exposure. Our investigation of organismal response to cadmium will enhance our understanding of the effects of stressful environments on a widely distributed and ecologically relevant aquatic organism, and will add valuable information to current ecotoxicology research.