By virtue of their enormous potential to produce type I interferons it is clear that plasmacytoid dendritic cells are major players in the host defense against viruses and various pathogens. Plasmacytoid dendritic cells were first identified in humans and very recently the mouse equivalents have been isolated. This review focuses, where possible, on a comparison between the cells in these two species. The mouse and human plasmacytoid DC are remarkably similar in surface phenotype and they display similar responses to pathogenic stimuli. The discovery of the mouse plasmacytoid dendritic cells has allowed for further biological properties of these cells to be investigated and it is now clear that they represent a long-lived family of cells that differentiate into novel dendritic cells upon microbiologic stimulation.