Development of new biochemical methods facilitated the isolation and analysis of viral glycoproteins and glycans. Use of plant lectins or sera from immunized animals as well as vaccinated patients facilitated purification of viral envelope proteins and enabled analysis of glycans at the individual protein level (Eisenberg et al. 1979; Wenske et al. 1982; Friedrichs and Grose 1984; Respess et al. 1984; Montalvo et al. 1985). Introduction of chemical glycan release from the peptides or sequential enzymatic deglycosylation enabled more precise characterization of viral glycan size and composition compared to pronase digests (Burke and Keegstra 1979; Rasilo and Renkonen 1979), and led to determination of type and structure of N- and O-linked glycans for many viruses (Pesonen 1979; Pesonen, Kuismanen et al. 1982; Pesonen, Ronnholm et al. 1982; Niemann et al. 1984). The subsequent introduction of reverse phase HPLC further facilitated glycopeptide analysis, allowing separation of larger glycopeptides, generated by digestion of proteins with proteases of defined specificity, such as trypsin. Subsequent enzymatic glycan release enabled N-glycan analysis on isolated glycopeptides (Rosner and Robbins 1982; Cohen et al. 1983; Hsieh et al. 1983), and demonstrated site-specific glycan microheterogeneity in different hosts (Hsieh et al. 1983). Development and advancement of mass spectrometry-based applications had a large impact on the analysis of glycans, which was quickly adopted in the virology field. More recent advances in mass spectrometry-based glycoprofiling and glycoproteomics of enveloped viruses are discussed in the following sections.