Antidepressants are one of the most commonly prescribed pharmaceutical classes for the treatment of psychiatric conditions. They act via modulation of brain monoaminergic signaling systems (predominantly serotonergic, adrenergic, dopaminergic) that show a high degree of structural conservation across diverse animal phyla. A reasonable assumption, therefore, is that exposed fish and other aquatic wildlife may be affected by antidepressants released into the natural environment. Indeed, there are substantial data reported for exposure effects in fish, albeit most are reported for exposure concentrations exceeding those occurring in natural environments. From a critical analysis of the available evidence for effects in fish, risk quotients (RQs) were derived from laboratory-based studies for a selection of antidepressants most commonly detected in the aquatic environment. We conclude that the likelihood for effects in fish on standard measured end points used in risk assessment (i.e. excluding effects on behavior) is low for levels of exposure occurring in the natural environment. Nevertheless, some effects on behavior have been reported for environmentally relevant exposures, and antidepressants can bioaccumulate in fish tissues. Limitations in the datasets used to calculate RQs revealed important gaps in which future research should be directed to more accurately assess the risks posed by antidepressants to fish. Developing greater certainty surrounding risk of antidepressants to fish requires more attention directed toward effects on behaviors relating to individual fitness, the employment of environmentally realistic exposure levels, on chronic exposure scenarios, and on mixtures analyses, especially given the wide range of similarly acting compounds released into the environment.