Malignant catarrhal fever (MCF) is a clinically noticeable, lethal disease of cloven-hoofed, ruminant mammals that include bison, African buffalo, water buffalo, antelopes, gazelles, sheep, goats, domestic cattle, and deer [1-3]. This disease has also been reported in pigs [4]. The causal agents for MCF are members of the MCF virus (MCFV) group that belongs to the genus Macavirus, subfamily Gammaherpesvirinae, family Herpesviridae [5]. MCF has a worldwide distribution and occurs sporadically and rarely in outbreaks. Clinically, MCF is characterized by high fever, hemorrhagic diarrhea, corneal opacity, and swelling of lymph nodes, usually culminating in death of the susceptible species. Similar to members of the Herpesviridae family, MCFV produces lifelong infection with establishment of latency. This chapter focuses on the two most prevalent viruses, alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2), within the genus Macavirus.