Hematopoietic stem cells (HSCs) exist in the bone marrow and circulate in the blood. In this issue, Massberg et al. (2007) report that HSCs also travel through the lymphatic system. Furthermore, migration of HSCs-which express Toll-like receptors-allows the recognition of pathogenic molecules in peripheral tissues thereby promoting the local generation of innate immune cells at the site of infection. © 2007 Elsevier Inc. All rights reserved.