Epstein-Barr virus (EBV) is an ancient virus, and has probably coevolved with its different hosts over the last 90-100 million years (McGeoch et al., 1995). With the ability to establish lifelong latency and intermittent reactivation after primary infection and with limited clinical symptoms in the majority of infected individuals, EBV has become ubiquitous in all human populations. Children in developing countries acquire the infection in the first few years of life, and universal seroconversion is often seen by ages 3-4 years, whereas infection in developed countries often is delayed until adolescence (de The et al., 1975; Haahr et al., 2004; Henle and Henle, 1967; Melbye et al., 1984a, b) (Figure 53.1). In some developed countries a bimodal infection rate, with peaks in children below 5 years and again after 10 years of age, has been described (Edwards and Woodroof, 1979; Henle and Henle, 1967; Lai et al., 1975). Oral EBV excretion between parents and infants, and from intimate partners in adolescence and early adulthood is the likely explanation for the observed bimodality (Crawford et al., 2002; Fleisher et al., 1979). EBV antibody titers in seropositive individuals vary according to age following a U-shaped pattern, with high titers among infants and in the elderly (above 50 years) (Glaser et al., 1985; Venkitaraman et al., 1985).