Recent studies indicate that the pharmaceutical fluoxetine, a selective serotonin reuptake inhibitor, is discharged in municipal wastewater treatment plant effluents to surface waters. Few data on environmental fluoxetine exposure and hazard to aquatic life are currently available in the literature. Here, we summarize information on fluoxetine detection in surface waters and review research on single-species toxicity test, Japanese medaka (Oryzias latipes) reproduction and endocrine function, and freshwater mesocosm community responses to fluoxetine exposure. Based on results from our studies and calculations of expected introduction concentrations, we also provide a preliminary aquatic risk characterization for fluoxetine. If standard toxicity test responses and a hazard quotient risk characterization approach are solely considered, little risk of fluoxetine exposure may be expected to aquatic life. However, our findings indicate that: (1) the magnitude, duration and frequency of fluoxetine exposure in aquatic systems requires further investigation; (2) mechanistic toxicity of fluoxetine in non-target biota, including behavioral responses, are clearly not understood; and (3) an assessment of environmentally relevant fluoxetine concentrations is needed to characterize ecological community responses.