The complement system is an ancient component of innate immunity, playing a crucial part in the defense against pathogens and maintaining homeostasis. Complement assures the opsonization of pathogens, facilitating phagocytosis. It generates potent mediators of inflammation recruiting and activating immune and stromal cells at the site of infection. Finally, it contributes to the direct killing of gram-negative bacteria by membrane perforation. The relevance of the complement system as an innate immune defense is evident from the increased susceptibility to infections in individuals with a deficiency of its components. As with every defensive mechanism, complement can turn against the host when dysregulated, causing severe organ damage. Therefore, understanding complement function is critical to understand human and animal homeostasis and defense against infection.