Neutrophils, an essential component of the innate immune system, are produced at a rate 10(11) cells/day and are consequently the most abundant leukocyte in the blood. These granulocytes have a relatively short half-life (6-8 h) in the blood, and as a result of the cytotoxic nature of their contents, it is critical that there are mechanisms in place for the efficient clearance of these effete cells from the circulation. Although macrophages of the reticuloendothelial system are positioned ideally to recognize and phagocytose apoptotic neutrophils in the circulation, this review challenges the current dogma that neutrophils are cleared primarily in the liver and spleen, presenting the evidence that the bone marrow is also an important site of neutrophil clearance under homeostatic conditions. Furthermore, a role for the CXCL12/CXCR4 chemokine axis in the trafficking of senescent neutrophils back to the bone marrow for clearance is described.