Kidney disease is often accompanied by activation of the complement system leading to complement deposition in the kidney. Activation may occur through the classical, lectin and/or alternative pathways and complement deposition may be demonstrated in acute and chronic renal diseases such as post-streptococcal glomerulonephritis, acute graft rejection, membranoproliferative glomerulonephritis, systemic lupus erythematosis, IgA nephropathy, thrombotic microangiopathies and vasculitides. The complement cascade results in release of proteins and peptides that promote opsonisation, inflammation, chemotaxis and anaphylaxis. All pathways ultimately result in formation of the terminal complement pathway and the membrane attack complex (C5b-9) leading to pore formation in the cell membrane and cytolysis. Regardless of the initiating event all pathways may undergo amplification via the alternative pathway's amplification loop. Between the fenestrated glomerular endothelium and the podocytes is the glomerular basement membrane (GBM) that functions as a filtration barrier between the circulation and the urinary space. The GBM is devoid of cell-bound complement regulators and thus dependent on soluble regulators. When soluble regulators are dysfunctional, due to mutations or neutralizing antibodies, complement will deposit in the kidney. This may explain why complement deposits in the kidney and why certain complement-mediated renal diseases recur after transplant. Systemic complement activation may also contribute to prothrombotic mechanisms occurring in certain kidney diseases.