Chemical communication of predation risk has evolved multiple times in fish species, with the conspecific alarm substance (CAS) contemporaneously being the most well understood mechanism. CAS is released after epithelial damage, usually when prey fish is captured by a predator, and elicits neurobehavioral adjustments in conspecifics which increase the probability of avoiding predation. As such, CAS is a partial predator stimulus, eliciting risk assessment-like and avoidance behaviors, and disrupting the predator sequence. The present paper reviews the distribution and putative composition of CAS in fish, and presents a model for the neural processing of these structures by the olfactory and the brain aversive systems. Applications of CAS in the behavioral neurosciences and neuropharmacology are also presented, exploiting the potential of model fish (e.g., zebrafish, guppies, minnows) on neurobehavioral research.