The large, complex genomes of herpesviruses document the high degree of adaptation of these viruses to their hosts. Not surprisingly, the methods developed over the past 30 years to analyse herpesvirus genomes have paralleled those used to investigate the genetics of eukaryotic cells. The recent use of bacterial artificial chromosome (BAC) technology in herpesvirus genetics has made their genomes accessible to the tools of bacterial genetics. This has opened up new avenues for reverse and forward genetics of this virus family in basic research, and also for vector and vaccine development.