Plasmacytoid dendritic cells (pDC) play a key role in antiviral immunity through their immense capacity to produce type I interferons (IFN) and other cytokines and through induction of antigen-specific T cell responses. Several reports have documented decreased numbers and reduced function of pDC in the circulation of HIV patients associated with progression to disease, indicating that pDC are likely to be important in control of HIV infection. The mechanism of pDC loss has not been determined and is difficult to address in natural infection of humans. As highlighted in this brief review, the study of pDC dynamics in simian immunodeficiency virus (SIV) infection of nonhuman primates paves the way to understanding the complex biology of this important innate system cell in HIV and other viral infections.