Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidases that catalyzes the cross-linking of collagens and elastin in the extracellular matrix (ECM). Expression of LOX is clinically correlated with metastasis and poor patient survival. Genetic, chemical or antibody inhibition of LOX significantly reduces metastases in various models of cancer. We have shown this occurs through preventing ECM remodeling at the primary site enhancing tumor cell invasion, and also through ECM remodeling at distant sites of future metastasis. This remodeling at pre-metastatic sites results in recruitment of bone marrow-derived cells and activation of host cells, creating niches permissive to metastasizing tumor cell colonization and growth. Moreover, we have found LOX to be responsible for fibrosis-enhanced metastasis, providing an important link between extracellular matrix homeostasis, fibrosis and cancer.