Glycosylation, one of the most common post-translational modifications in mammalian cells, impacts many biological processes such as cell adhesion, proliferation and differentiation. As the most abundant glycoprotein in human serum, immunoglobulin G (IgG) plays a vital role in immune response and protection. There is a growing body of evidence suggests that IgG structure and function are modulated by attached glycans, especially N-glycans, and aberrant glycosylation is associated with disease states. In this chapter, we review IgG glycan repertoire and function, strategies for profiling IgG N-glycome and recent studies. Mass spectrometry (MS) based techniques are the most powerful tools for profiling IgG glycome. IgG glycans can be divided into high-mannose, biantennary complex and hybrid types, modified with mannosylation, core-fucosylation, galactosylation, bisecting GlcNAcylation, or sialylation. Glycosylation of IgG affects antibody half-life and their affinity and avidity for antigens, regulates crystallizable fragment (Fc) structure and Fcγ receptor signaling, as well as antibody effector function. Because of their critical roles, IgG N-glycans appear to be promising biomarkers for various disease states. Specific IgG glycosylation can convert a pro-inflammatory response to an anti-inflammatory activity. Accordingly, IgG glycoengineering provides a powerful approach to potentially develop effective drugs and treat disease. Based on the understanding of the functional role of IgG glycans, the development of vaccines with enhanced capacity and long-term protection are possible in the near future.