•Complement activation in IgA nephropathy is a major pathogenic process.•Lectin and alternative pathway activation are the main complement routes involved in IgA nephropathy.•In IgA nephropathy, variation in IgA consists of isoforms, glycoforms and presence of IgA containing immune complexes.•Variations in IgA might be responsible for complement activation in both systemic and kidney compartments.•Novel complement inhibitory strategies are currently tested in phase II or III trials in IgA nephropathy. IgA Nephropathy (IgAN) is the main cause of primary glomerulonephritis, globally. This disease is associated with a wide range of clinical presentations, variable prognosis and a spectrum of histological findings. More than fifty years after its first description, this heterogeneity continues to complicate efforts to understand the pathogenesis. Nevertheless, involvement of the complement system in IgAN was identified early on. Dysfunction of the immunoglobulin A (IgA) system, the principal offender in this disease, including modification of isoforms and glycoforms of IgA1, the nature of immune complexes and autoantibodies to galactose deficient IgA1 might all be responsible for complement activation in IgAN. However, the specific mechanisms engaging complement are still under examination. Research in this domain should allow for identification of patients that may benefit from complement-targeted therapy, in the foreseeable future.