The present review focuses on recent development in our understanding of the molecular mechanisms of DNA replication of herpes simplex virus 1 (HSV-1). Progress made in the characterization of the early events of viral DNA synthesis and of virus-host cell interactions, especially in the context with the formation of viral DNA replication sites, is highlighted. An up-dated overview is presented on important stages of lytic infection cycle, such as virion entry, viral DNA synthesis, viral DNA cleavage and packaging into preformed capsids; and maturation (nucleocapsid envelopment) and egress of virions. Many novel interactions are discussed that extend not only our knowledge of the biology of this virus but may represent possible new targets for antiherpesviral therapy.