Dendritic cells (DCs) play a vital role in the generation of immune responses, participating both in innate immunity as well as in the initiation of adaptive immunity. However, study of this rare cell population in vivo has been hampered by their low frequency as well as by inadequate means to track antigen-bearing DCs. Our laboratory has developed a novel strategy to genetically tag these DCs in the skin, and to monitor their migration from the periphery to the draining lymph nodes. These studies have provided new insights into the frequency of DC migration, the longevity of DCs in the lymphoid organs, as well as the ability of these DCs to function as antigen-presenting cells. Furthermore, the potential applications of this technique include the ability to evaluate DC function after silencing of specific genes.