Monitoring of freshwater quality and its potential sudden contamination is integral to human health, sustainable economic development and prediction of pollutant impact on aquatic ecosystems. Although there have been significant advances in technologies for automated sampling and continuous analysis of water physicochemical parameters, the current capabilities for real-time warning against rapidly developing unknown mixtures of chemical hazards are still limited. Conventional chemical analysis systems are not suitable for assessing unknown mixtures of chemicals as well as additive and/or synergetic effects on biological systems. From the perspective of neurotoxicology the acute exposures to chemical agents that affect nervous system and can enter the freshwater supplies accidentally or as a result of deliberate action, can only be reliably assessed using appropriate functional biological models. In this regard real-time biological early warning systems (BEWS), that can continuously monitor behavioural and/or physiological parameters of suitable aquatic bioindicator species, have been historically proposed to fill the gap and supplement conventional water quality test strategies. Alterations in sub-lethal neuro-behavioural traits have been proven as very sensitive and physiologically relevant endpoints that can provide highly integrative water quality sensing capabilities. Although BEWS are commonly regarded as non-specific and lacking both quantitative and qualitative detection capabilities, their advantages, if properly designed and implemented, lie in continuous sensing and early-warning information about sudden alteration in water quality parameters. In this work we review the future prospects of real-time biological early warning systems as well as recent developments that are anchored in historical successes and practical deployment examples. We concentrate on technologies utilizing analysis of behavioural and physiological endpoints of animal bioindicators and highlight the existing challenges, barriers to future development and demonstrate how recent advances in inexpensive electronics and multidisciplinary bioengineering can help revitalize the BEWS field.