Tumor cell dissemination to distant organ sites is a complex process involving multiple cell types, soluble growth factors, adhesion receptors, and tissue remodeling. A new study in this issue of Cancer Cell shows that MMP9-expressing tumor-associated macrophages play a key role in prepping premetastatic sites for eventual malignant cell growth in a manner dependent upon vascular endothelial growth factor receptor-1 (VEGFR-1).