Plasmacytoid dendritic cells (pDC) have emerged as a principal subset of dendritic cells in both human and mouse. PDC morphology, surface markers, their migration in vivo and the ability to rapidly produce large amounts of type I interferons (IFN-alpha/beta) in response to toll like receptor (TLR) triggering sets them apart from other dendritic cell subsets. This review highlights the features that make pDC uniquely able to sense and respond to viral infection.