The coexistence of viruses and their hosts implies constant and mutual evolutionary pressure. In addition to the fundamental systems necessary for viruses to replicate and spread, viruses have developed accessory systems to escape killing by the host's immune system. Herpesviruses have been coevolving with their hosts over millions of years and are exquisitely well adapted to their respective partners. Biological criteria have long been used to subdivide the family Herpesviridae into three subfamilies, namely Alpha-, Beta-, and Gammaherpesvirinae. Members of the Alphaherpesvirinae have a narrow in vivo host range, a short replication cycle, and the capacity to establish lifelong, latent infections, primarily but not exclusively in neurons of sensory ganglia (50). Their linear, double-stranded DNA genomes vary between 124 and 177 kbp in length and generally consist of regions of unique sequences flanked by direct or inverted repeat sequences. The subfamily includes human pathogens as well as a number of animal viruses of considerable agricultural and economic importance (Table (Table1).1). The human pathogens herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) are the causative agents of cold sores, genital ulcerous disease, and chickenpox/shingles, respectively. Some of the animal herpesviruses can cause diseases with potentially devastating economic consequences. Infection with equine herpesvirus type 1 (EHV-1) results in respiratory disease, abortion, and neurological disorders; bovine herpesvirus type 1 (BHV-1) leads to respiratory infections and abortions in cattle; pseudorabies virus (PRV) (suid herpesvirus 1) infection (Aujeszky's disease) is characterized by respiratory and neurological disorders, abortion, and infertility in swine; and Marek's disease virus (MDV), an oncogenic alphaherpesvirus, causes massive immunosuppression and invariably lethal T-cell lymphomas in unvaccinated chickens.