Abstract: In the last 10 years, the human cell-surface molecule, CD46, has evolved from ‘just another complement regulator’ to a receptor for a striking array of pathogens. CD46 not only protects cells from complement-mediated attack and facilitates infection by a large number of pathogens, but also exerts complex effects on cellular immune function. It has been proposed that CD46 links innate and adaptive immunity by affecting cellular immune function in response to complement binding, and the role of CD46 in the pathogenesis of many infectious pathogens is now the subject of intense investigation. So far, the flood of information that implicates CD46 in modifying a host response to measles, Neisseria, human herpes virus 6, and pathogens that activate complement has not yet been matched with a comprehensive understanding of the molecular mechanisms by which CD46 affects immune function. This review summarizes the evidence that points to a significant role for CD46 in a range of pathological processes and describes how CD46 might exert its effects by altering signal transduction and antigen presentation pathways.