Metastasizing tumor cells face numerous physical and biological barriers as they traverse the circulation to their metastatic niche, which can itself be antagonistic to the establishment of metastatic lesions. The cover depicts a 3D reconstruction of serial lung tissue sections, with vasculature labeled in red and cell nuclei in blue. Melanoma cells labeled with green fluorescent CMFDA dye appear yellow within the circulation, or green if they have successfully extravasated into the lung tissue. In their article on page 2096, Arif, Huang, and colleagues demonstrate that inflammation of the lung tissue mediated by monocyte-derived macrophages conditions the lung metastatic niche and promotes the development of metastatic lesions. This article is also featured in this issue's Highlights on page 1971.