Plasmacytoid dendritic cells (PDCs) or natural interferon-producing cells, function as the body's innate defense against viral infections. As discussed here, they may play additional roles in response to bacterial pathogens and may have the capacity to induce different type of T-cell responses depending on what signals they receive. The discovery of routine PDCs will allow for the design of models to study viral immunobiology in vivo and to determine their function in various diseases that involve plasmacytoid dendritic cells, such as selected leukemias, lymphomas, allergies, different autoimmune conditions, and their possible role in inducing and maintaining tolerance.