Summary: IgA nephropathy, the most common primary glomerulonephritis in the world and a frequent cause of end-stage renal disease, is characterized by typical mesangial deposits of IgA1, as described by Berger and Hinglaise in 1968. Since then, it has been discovered that aberrant IgA1 O-glycosylation is involved in disease pathogenesis. Progress in glycomic, genomic, clinical, analytical, and biochemical studies has shown autoimmune features of IgA nephropathy. The autoimmune character of the disease is explained by a multihit pathogenesis model, wherein overproduction of aberrantly glycosylated IgA1, galactose-deficient in some O-glycans, by IgA1-secreting cells leads to increased levels of circulatory galactose-deficient IgA1. These glycoforms induce production of autoantibodies that subsequently bind hinge-region of galactose-deficient IgA1 molecules, resulting in the formation of nephritogenic immune complexes. Some of these complexes deposit in the kidney, activate mesangial cells, and incite glomerular injury. Thus, galactose-deficient IgA1 is central to the disease process. In this article, we review studies concerning IgA1 O-glycosylation that have contributed to the current understanding of the role of IgA1 in the pathogenesis of IgA nephropathy.