Despite mounting evidence of pleiotropic ecological risks, the understanding of the eco-neurotoxic impact of most industrially relevant chemicals is still very limited. In particularly the acute and chronic exposures to industrial pollutants on nervous systems and thus potential alterations in ecological fitness remain profoundly understudied. Since the behavioral phenotype is the highest-level and functional manifestation of integrated neurological functions, the alterations in neuro-behavioral traits have been postulated as very sensitive and physiologically integrative endpoints to assess eco-neurotoxicological risks associated with industrial pollutants. Due to a considerable backlog of risk assessments of existing and new production chemicals there is a need for a paradigm shift from high cost, low throughput ecotoxicity test models to next generation systems amenable to higher throughput. In this review we concentrate on emerging aspects of laboratory-based neuro-behavioral phenotyping approaches that can be amenable for rapid prioritizing pipelines. We outline the importance of development and applications of innovative neuro-behavioral assays utilizing small aquatic biological indicators and demonstrate emerging concepts of high-throughput chemo-behavioral phenotyping. We also discuss new analytical approaches to effectively and rapidly evaluate the impact of pollutants on higher behavioral functions such as sensory-motor assays, decision-making and cognitive behaviors using innovative model organisms. Finally, we provide a snapshot of most recent analytical approaches that can be applied to elucidate mechanistic rationale that underlie the observed neuro-behavioral alterations upon exposure to pollutants. This review is intended to outline the emerging opportunities for innovative multidisciplinary research and highlight the existing challenges as well barriers to future development.