The prognosis for cancer patients with metastatic disease remains poor. For cancer to metastasize from a primary tumor to distinct sites in the body, both the extracellular matrix and basement membrane--physiological barriers whose primary structural constituent is collagen--must be degraded to allow the passage of tumor cells. Collagen has long been assumed to be a passive background upon which the biochemical events of metastasis take place, but recent experimental developments instead point to a novel active role for collagen in the immune response to metastasis. Along with a new hypothesis for the mechanism of collagen degradation, these data suggest innovative approaches to prevent the spread of cancer from the primary tumor site.