Abstract Infectious diseases represent a major health problem. Based on the limited efficacy of existing drugs and vaccines and the increasing antibiotic resistance new strategies are needed to fight infectious diseases. A better understanding of pathogen–host interaction is one important aspect to identify new virulence factors and antimicrobial and anti-inflammatory compounds utilized by pathogens represent an additional source for effective anti-inflammatory compounds. Complement forms a major defense line against invading microbes, and pathogens have learned during evolution to breach this defense line. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. Pathogens mimic host surfaces and bind host complement regulators. Similarly pathogens utilize a number of complement inhibitory molecules which help to evade complement attack and which display anti-inflammatory activity. The molecular identification of these molecules, as well as the functional characterization of their roles at the pathogen–host interface is an important and emerging field of infection biology. In addition, pathogens utilize multiple sets of such regulators as redundancy and multiplicity is important for immune and complement evasion. Here we summarize the current scenarios of this emerging field which identifies multiple virulence factors and complement evasion strategies, but which at the same time reveals common mechanisms for immune and complement defense.