Pharmaceutical pollution is a global environmental problem. Of particular concern are psychotherapeutic drugs with the capacity to adversely impact exposed wildlife at extremely low concentrations. Here, we investigate the impacts of the antidepressant fluoxetine—one of the most commonly prescribed psychotherapeutic drugs and one of the most frequently detected in the environment—on the behaviour of aquatic wildlife. More specifically, we address the impacts of fluoxetine on antipredator behaviours of the Eastern mosquitofish (Gambusia holbrooki) using two ecologically realistic dosages. We found that fluoxetine exposure at the lower dosage resulted in increased activity levels irrespective of the presence or absence of a predator. Additionally, fluoxetine-exposed fish, at both concentrations, entered the predator ‘strike zone’ more rapidly. In a separate experiment, we showed that at just 8 ng/L fluoxetine exposure reduced freezing behaviour, a typical antipredator strategy, following a simulated predator strike. To date, this is the lowest concentration reported to affect the behaviour of wildlife. Together, these findings suggest that exposure to psychiatric pollutants, like fluoxetine, can alter antipredator behaviour in fish at field detected concentration and, in doing so, may impact the fitness of exposed wildlife.