The heavy glycosylation of HIV envelope constitutes a strong defense mechanism for the virus to evade host immune response, which accounts for a major barrier for HIV vaccine development. Nevertheless, the identification of a number of glycan-dependent broadly HIV-neutralizing antibodies from HIV-infected individuals, including 2G12, PG9, PG16, PGT121-123, PGT125-128, and PGT135, strongly suggests that the defensive viral 'glycan shield' can be important targets of vaccines. The novel glycan recognition mode exhibited by these antibodies provides new templates for immunogen design. This review highlights recent work on the characterization of the glycan-dependent epitopes of these neutralizing antibodies and recent advances in the synthesis of the relevant carbohydrate antigens for HIV vaccine design.