Mutations in Factor H, MCP and Factor I have established that aHUS is a disease of complement dysregulation. These findings give hope that complement inhibition may be of therapeutic benefit in this condition. In the near future, we expect mutations to be found in other complement genes. This work has major implications for how we think about syndromes involving essentially any type of tissue injury where the complement cascade is activated (autoantibodies, immune complexes, ischemia/reperfusion injury, sepsis and many others). For a given degree of injury, individuals with defects in Factor H, MCP and Factor I, even if heterozygous, will likely be at increased risk for more severe tissue damage because they cannot appropriately regulate C3 activation and amplification.