Neurophils are a key component of the innate immune response and a major contributor to inflammation. Accordingly, their number in the blood is tightly controlled. Neutrophils are normally produced exclusively in the bone marrow, and their release into the blood is tightly regulated to maitain homeostatic levels in the blood. Herein, recent evidence is reviewed showing that stromal cell-derived factor-1 (SDF-1, CXCL12) plays a key role in regulating neutrophil trafficking in the bone marrow. Moreover, studies are discussed showing that granulocyte colony-stimulating factor, primarily through regulation of SDF-1 expression in the bone marrow, plays an essential role in maitaining neutrophil homeostasis in the blood.