Herpes simplex virus (HSV) is an important pathogenic agent that causes recurrent oral and genital lesions, blindness and encephalitis. It is a member of the family Herpesviridae, which contains three subfamilies (alpha- beta- and gammaherpesvirinae) whose members infect humans to cause a variety of ailments, from benign rashes to nasopharyngeal carcinoma. Although this review focuses on HSV, the assembly steps that occur in the nucleus and the proteins involved are highly conserved among all family members, which suggests that antiviral agents that block these steps might be effective against many different herpesviruses and their associated diseases. Despite this potential, a broadly effective compound has yet to be realized, in part because many of the processes are only poorly understood in sufficient molecular detail. This review outlines these intranuclear assembly steps and illustrate potential and existing antiviral strategies that exploit them.