Plasmacytoid dendritic cells (pDCs) are specialized producers of type I interferons (IFNs) that respond to most viruses. Because of their antiviral activity and regulatory functions in innate and adaptive immunity, type I IFNs are important not only for antiviral resistance but also in other types of infections and in immune pathology. Here we discuss recent data that begin to reveal the unique molecular mechanisms underlying the remarkably rapid and efficient type I IFN production by pDCs.