Among the many pressures that marine organisms face, intense competition and predation have contributed to the evolution of chemical defenses and the ability to sense chemical cues. Chemical ecologists have long sought to understand the identities, functions, and consequences of these compounds in the marine environment. However, traditional approaches to connect naturally occurring chemical compounds with ecological outcomes have often been unsatisfactory. We have developed a metabolomics-based strategy to take advantage of the natural variation in production of chemical cues across different environmental conditions towards identifying ecologically important waterborne molecules and their effects on organism behavior and physiology, tested using predator-prey interactions within Georgia estuaries. As expected, marine organisms respond to a diversity of chemical species in their watery worlds, exhibiting dramatic behavioral and physiological changes when exposed to predators and competitors.