Measles virus (MV) was isolated in 1954 (Enders and Peeble 1954). It is among the most contagious of viruses and a leading cause of mortality in children in developing countries (Murray and Lopez 1997; Griffin 2001; Bryce et al. 2005). Despite intense research over decades on the biology and pathogenesis of the virus and the successful development in 1963 of an effective MV vaccine (Cutts and Markowitz 1994), cell entry receptor(s) for MV remained unidentified until 1993. Two independent studies showed that transfection of nonsusceptible rodent cells with human CD46 renders these cells permissive to infection with the Edmonston and Halle vaccine strains of measles virus (Dorig et al. 1993; Naniche et al. 1993). A key finding in these investigations was that MV binding and infection was inhibited by monoclonal and polyclonal antibodies to CD46. These reports established CD46 as a MV cell entry receptor. This chapter summarizes the role of CD46 in measles virus infection.