New informatics capabilities and computational and mathematical modelling techniques, used in combination with highly sensitive molecular biology and mechanistic chemistry approaches, are transforming the way in which we assess the safety of chemicals and products. In recent years, good progress has been made in replacing some of the animal tests required for regulatory purposes with methods using cells and tissues in vitro . Nevertheless, big scientific challenges remain in developing relevant non-animal models able to predict the effects of chemicals which are absorbed systemically. The greatest breakthroughs in non-animal approaches for chemical safety assessment will most likely result from continued multi-disciplinary research investment in predictive (integrative and systems) biology. Some of our current research in this area is described in the present article.