Chemical signaling in the plankton modulates myriad ecological predator-prey interactions. In turn, these relationships influence planktonic community structure and ultimately global processes including carbon fixation and biogeochemical cycling. Our review highlights the roles of several influential metabolites in the plankton, beginning with interactions between harmful algal bloom-forming dinoflagellates in the genus Alexandrium and their predators. This well-characterized system provides a model for probing co-evolution between predators and chemically defended plankton prey. Other plankton-produced compounds, polyunsaturated aldehydes (PUAs) and dimethyl sulphoniopropionate (DMSP), may act as activated defenses against predators. Although the effect of PUAs on copepods remains controversial, these compounds have cascading impacts, including the potential to influence ocean carbon sequestration. Like PUAs, DMSP and its degradation products are important in predator-prey interactions, with impacts across multiple scales. They are foraging cues for seabirds, components in the global sulfur cycle, and influencers of global climate. It is essential to understand how these ubiquitous small molecules mediate predator-prey interactions in this critical group of organisms. Future studies should provide an evolutionary context to these interactions, identify ecologically relevant compounds, and elucidate the roles of these compounds in natural communities to better understand the response of marine systems to a changing global climate.