There is a need for a more effective Developmental Neurotoxicity (DNT) screening which is scientifically driven by the fact that the developing nervous system might be more sensitive to exposures to some hazardous chemical. Additional concern comes from the recent societal concerns that toxic chemicals can contribute to the prevalence of neurodevelopment disabilities. Consequently, hazard identification and actions to reduce exposure to these chemicals is a priority in chemical risk assessment. To reach this goal a cost-efficient testing strategy based on a reliable in-vitro testing battery should be developed. Although this goal is representing a huge challenge in risk assessment, available data and methodologies are supporting the ultimate aim of developing a predictive model able to respond to different regulatory based problem formulations.