Advances in analytical and diagnostic assays based on novel nucleic acid analyses techniques have revolutionized the application of molecular differentiation of microorganisms. Phenotypic typing schemes are now broadly supplemented by new genotyping methods which allow a more refined and detailed differentiation of closely related microorganisms, bacterial strains, isolates and pathogens on the DNA level. Bio-, sero- and phagetyping, antibiotic susceptibility tests, immunoblotting as well as multilocus enzyme- or polyacrylamide gel electrophoresis are now supported by the analysis of plasmid or chromosomal DNA restriction profiles, ribotyping, pulsed-field gel electrophoresis and polymerase- or ligase-chain reaction-based methods or direct sequencing technique to differentiate microorganisms. Some of these molecular techniques are also used in the field of virology to analyse and differentiate closely related sub- or genotypes. Few examples for the analysis and investigation of these usually small genomes will also be given.