Specific virus-receptor interactions are important determinants in the pathogenesis of viral infections, influencing the location and initiation of primary infection as well as the viral spread to other target organs in the postviremic phase. Coxsackieviruses of group B (CVB) specifically interact with at least two receptor proteins, the coxsackievirus-adenovirus receptor (CAR) and the decay-accelerating factor (DAF), and cause a broad spectrum of diseases, including acute and chronic myocarditis. In the human heart, CAR is predominantly expressed in intercalated discs, regions of utmost importance for the functional integrity of the heart. Since DAF is abundantly expressed in epithelial and endothelial cells, interaction of cardiotropic CVB with the DAF coreceptor protein, in addition to CAR, could therefore be advantageous to the virus by enhancing viral entry into the heart.