NIPCs have had a long history of study, with the first observations of peripheral blood cells with IFN-producing capacity being made approximately 20 years ago. Over the past three years with the identification of NIPCs as plasmacytoid dendritic cells, an enormous amount has been learned about their function in both innate and adaptive immunity and their dysregulation in certain viral infections such as HIV infection and in autoimmunity. Further studies of their mechanisms of IFN-alpha induction, of their distribution and in vivo function are required. It is anticipated that a further understanding of the PDC will lead to the ability to specifically manipulate these cells in human disease.