The ability to predict and then mitigate potential health effects is crucial for sustainability of nanotechnology, yet approaches to testing must evolve to provide both specificity and efficiency whilst reducing the burden of animal testing. To provide risk assessment with adequate information, a complementary strategy relying on the use of exposure biomarkers can be envisaged as part of a holistic approach to supporting effective risks management systems. Candidate biomarkers should be further validated in controlled human studies. This article discusses the meaning and role of biomonitoring as key component of a comprehensive toolbox of nanosafety.