Genetics, cell biology, and whole-genome sequencing of pathogens have changed dramatically the opportunities to investigate the epidemiology, pathogenesis, diagnosis, and control of microbial diseases. For example, recombinant DNA and PCR are powerful tools used to isolate genes whose role in pathogenicity can be investigated in biologically relevant virulence assays. Vaccines that target one or more of these genes can then be developed. Complete genome sequences of microbes provide an inventory of the genes encoding every virulence factor and potential immunogen. Candidate vaccines can be selected and developed using various approaches, including the recent innovation of immunisation with nucleic acids. Although many successful vaccines have been and will continue to be developed through empirical approaches, molecular microbiology provides a rational basis for discovery, development, and implementation of safer, more effective and, potentially cheaper vaccines.