The role of complement in human autoimmune, inflammatory, and infectious diseases is reviewed, focusing on clinical applicability. A typical case is presented in which serum testing for C3 and C4 is performed to help assess a syndrome with a broad differential diagnosis. The review includes a discussion of complement deficiency states, consumption of complement by diseases characterized by immune‐complex formation and deposition, usefulness and interpretation of laboratory tests for complement, and development of drugs targeting specific components of the complement pathway for a growing number of indications.