The varicella-zoster virus (VZV) genome contains at least 70 genes, and all but six have homologs in herpes simplex virus (HSV). Cosmids and BACs corresponding to the VZV parental Oka and vaccine Oka viruses have been used to "knockout" 34 VZV genes. Seven VZV genes (ORF4, 5, 9, 21, 29, 62, and 68) have been shown to be required for growth in vitro. Recombinant viruses expressing several markers (e.g., beta-galactosidase, green fluorescence protein, luciferase) and several foreign viral genes (from herpes simplex, Epstein-Barr virus, hepatitis B, mumps, HIV, and simian immunodeficiency virus) have been constructed. Further studies of the VZV genome, using recombinant viruses, may facilitate the development of safer and more effective VZV vaccines. Furthermore, VZV might be useful as a vaccine vector to immunize against both VZV and other viruses.