The complement system was discovered almost a century ago as an important effector in antibody-dependent killing of microorganisms. Since this early period much was learned about the biochemistry and structure of complement proteins and their function in mediating inflammation. More recently, a prominent role for complement was identified in linkage of innate and adaptive immunity. In this review, I will discuss our current understanding of the importance of complement in enhancing the humoral immune response to both model antigens and pathogens. As discussed below, it is evident that the complement system participates in marking of “foreign” pathogens and “presenting” them to B cells in a manner that enhances both antibody production and long-term memory. In this special issue of Vaccine, we see examples of how complement is critical in the immune response to bacterial and viral pathogens. Moreover, the finding that most organisms have co-evolved proteins to evade complement detection underscores its importance in host protection.