Historically, herpesviruses and togaviruses were some of the first viruses investigated for modification with carbohydrates, which led to important findings regarding general aspects of viral glycosylation. Early methods of analysis were based on monitoring the incorporation of radioactively labeled monosaccharides and amino acids into newly synthesized viral proteins during infection (Keller et al. 1970; Spear and Roizman 1970; Kim et al. 1976). It was thereby established that viral protein glycosylation took place at the cellular membranes and not the cytoplasmic compartment (Spear and Roizman 1970). Early glycoprofiling experiments utilized pronase digestion of labeled glycoproteins followed by gel filtration, which allowed separation of the short glycopeptides, bearing different glycan moieties (Honess and Roizman 1975; Schwarz et al. 1977). Moreover, differentially labeled sugars were used to provide insight into the putative composition of individual glycan structures (Sefton 1975). An important conclusion based on such experiments was that the extent of sugar incorporation into individual viral proteins differed depending on the infected cell type (Keller et al. 1970), establishing that viruses are dependent on the host glycosylation machinery. Use of glycosylation inhibitors, such as tunicamycin, 2-deoxy-d-glucose and glucosamine, provided additional insights into regulation of glycan synthesis, its impact on viral replication, and showed that glycosylation of viral proteins is critical for infectivity and cell–cell fusion (Knowles and Person 1976; Leavitt et al. 1977; Olofsson and Lycke 1980; Herrler and Compans 1983; Lambert and Pons 1983; Mann et al. 1983). Studies in cell lines deficient for specific glycosyltransferases or intracellular transport inhibitors provided additional means for investigating biological consequences of disrupted glycan synthesis and maturation, respectively (Campadelli-Fiume et al. 1982; Serafini-Cessi, Dall’Olio, Scannavini, Campadelli-Fiume et al. 1983; Edwardson 1984).