CD46 (also known as membrane cofactor protein or MCP) is a regulator of complement activation that is expressed in most or all human nucleated cell types. CD46 was initially identified as binding and inactivating C3b and C4b complement products, a process protecting human cells from lysis by autologous complement (18). It also serves as a receptor for several human pathogens: an enveloped RNA virus (measles virus [MV]), an enveloped DNA virus (human herpesvirus 6), a nonenveloped DNA virus (adenovirus of different serotypes), and two types of bacteria (Streptococcus pyogenes and pathogenic Neisseria)(13, 27). Moreover, bovine CD46 was recently shown to serve as a receptor for bovine viral diarrhea virus (BVDV), an enveloped RNA virus. That six different pathogens selected the same molecule as a port of cell entry is of interest not only for microbiologists and immunologists, who wonder what makes CD46 such a seductive molecule, but also for gene therapists, who are seeking opportunities for targeting disease sites.