There is a large body of experimental and clinical evidence that complement activation contributes to glomerular injury in multiple different diseases. However, the underlying mechanisms that trigger complement activation vary from disease to disease. Immune complexes activate the classical pathway of complement in many types of glomerulonephritis, whereas the alternative pathway and mannose-binding lectin pathways are directly activated in some diseases. Eculizumab is an inhibitory antibody to C5 that has been approved for the treatment of atypical hemolytic uremic syndrome, and case reports suggest that it is also effective in other types of glomerulonephritis. Furthermore, new complement-inhibitory drugs are being developed that target additional proteins within the complement cascade, raising the possibility of blocking the specific complement proteins involved in a given disease. This review examines the rationale for targeting different proteins within the complement cascade, the new anti-complement drugs currently in development and some of the challenges that investigators will face in bringing these drugs to the clinic.