The International Council of Chemical Associations’ Long-Range Research Initiative (ICCA-LRI) sponsored a workshop, titled Twenty-First Century Approaches to Toxicity Testing, Biomonitoring, and Risk Assessment, on 16 and 17 June 2008 in Amsterdam, The Netherlands. The workshop focused on interpretation of data from the new technologies for toxicity testing and biomonitoring, and on understanding the relevance of the new data for assessment of human health risks. Workshop participants articulated their concerns that scientific approaches for interpreting and understanding the emerging data in a biologically relevant context lag behind the rapid advancements in the new technologies. Research will be needed to mitigate these lags and to develop approaches for communicating the information, even in a context of uncertainty. A collaborative, coordinated, and sustained research effort is necessary to modernize risk assessment and to significantly reduce current reliance on animal testing. In essence, this workshop was a call to action to bring together the intellectual and financial resources necessary to harness the potential of these new technologies towards improved public health decision making. Without investment in the science of interpretation, it will be difficult to realize the potential that the advanced technologies offer to modernize toxicity testing, exposure science, and risk assessment.