The extraordinary plasticity of bacterial genomes raises concerns about the adequacy of laboratory-adapted reference strains for the study of "real-world" pathogenesis. Some laboratory strains have been sub-cultured for decades since their first isolation and might have lost important pathophysiological characteristics. Evidence is presented that bacteria rapidly adapt to in vitro conditions. Genomic differences between laboratory reference strains and corresponding low-passage clinical isolates are reviewed. It appears that no bacterial strain can truly represent its species. For DNA microarray and proteomic studies, this limitation might be overcome by the summation of individual genomes to produce a species-specific virtual supragenome.