Cytomegalovirus (CMV) infection is characterized by host immunosuppression and multiorganic involvement. CMV-infected dendritic cells (DC) were recently shown to display reduced immune functions, but their role in virus dissemination is not clear. In this report, we demonstrated that CMV could be captured by DC through binding on DC-SIGN and subsequently transmitted to permissive cells. Moreover, blocking DC-SIGN by specific antibodies inhibited DC infection by primary CMV isolates and expression of DC-SIGN or its homolog DC-SIGNR rendered susceptible cells permissive to CMV infection. We demonstrated that CMV envelope glycoprotein B is a viral ligand for DC-SIGN and DC-SIGNR. These results provide new insights into the molecular interactions contributing to cell infection by CMV and extend DC-SIGN implication in virus propagation.