ONLINE COVER Critical Crossroads. This month's cover features an immunofluorescence image of a murine tumor-draining lymph node containing metastatic melanoma cells (GFP-expressing YUMM1.7 cells; cyan). Tumor cells reach the tumor-draining lymph node via afferent lymphatic vessels that intersect with the subcapsular and interfollicular sinuses (sinus-lining lymphatic endothelial cells stained with anti-LYVE-1; orange). The sinuses run around and between B cell follicles (B cells stained with anti-B220; purple). A Review by du Bois, Heim, and Lund summarizes our current understanding of the structural biology of tumor-draining lymph nodes, how they are primed to receive metastasizing tumor cells, and their unique impact on prognosis and immunotherapy.