The concept or notion of virulence factor–activity relationships (VFAR) is an approach for identifying an analogous process to the use of qualitative structure–activity relationships (QSAR) for identifying new microbial contaminants. In QSAR, it is hypothesized that, for new chemical contaminants, their potential acute or chronic toxicity may be reasonably estimated on the basis of structural relationships to other known toxic contaminants. Thus the parallel that is being attempted for pathogenic microorganisms is that known virulence factors may be used as predictors for identifying undiscovered pathogens and microbial causes of emerging diseases. Advances in molecular biology, genomics and proteomics have led the Committee on Drinking Water Contaminants of the National Research Council, as requested by the EPA, to recommend the VFAR approach as a potentially more systematic and scientific process for the selection of microorganisms for inclusion in the Contaminant Candidate List (CCL).