The link between chronic exposure to multiple environmental contaminants, biotic or abiotic, such as air pollutants, endocrine disruptors, medicines, biocides and micro-organisms, and the progress observed in epidemiological studies of multifactorial diseases such as metabolic, cardiovascular, cancer and multi-drug-resistant infections is a major public health concern. While the share of genetic factors of susceptibility or predisposition to them is becoming more and more known due to the dramatic advances in molecular biology techniques, the share of the environment remains more complex to assess. This complexity results from the multiplicity of sources of exposure (e.g. diet, air, occupational or domestic environment), their very low concentration, but above all from the multiplicity of chemical, biological and physical factors to which we are exposed throughout our lives and from the multiplicity of toxic mechanisms involved. The health impact of such a chronic multi-exposure at low doses thus far remains largely unknown. Similarly, bacteria can be regularly exposed to chemical contaminants. The recent epidemiology of infectious diseases reveals the importance of the environment and global changes in the acquisition of virulence and/or the emergence of resistance in micro-organisms to environmental pollutants and decontamination methods.In this context, the assessment of the health risk associated with these multi-exposures is based on effective and biologically relevant exposure models and effective global analysis techniques to capture multi-exposures, including trace levels. As proposed by C. Wild in his famous concept of exposure, the risk assessment is based on the combination of markers at different levels: external dose, internal dose, biologically active dose, markers of early biological effects, phenotypic markers, throughout the life of the individual.