Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O‐linked oligosaccharides (O‐glycans), which are conjugated through serine or threonine residues. During various biological processes, including T‐cell activation, a tetrasaccharide on the T‐cell surface is dramatically converted to a branched hexasaccharide, called core2 O‐glycan. The same structural change in O‐glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott‐Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O‐glycans in immune responses show that this is a biologically significant change. In particular, core2 O‐glycans expressed on the cell surface reduce cell–cell interactions, thereby regulating immune responses. Furthermore, core2 O‐glycan is a key backbone structure in forming selectin ligands. Thus, O‐linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O‐glycans in immunological processes. BioEssays 23:46–53, 2001. © 2001 John Wiley & Sons, Inc.