Remodelling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. The tight control of biochemical and biomechanical properties of the ECM and the ongoing remodelling of the ECM is critical in maintaining correct organ function. When this remodelling becomes excessive or uncontrolled, life-threatening pathological conditions such as cancer can result. In this chapter, we focus on the importance and complexity of cell-ECM interactions in determining correct cell behaviour under normal conditions and what happens when it all goes wrong in situations of cancer. We discuss the pathogenesis of breast cancer initiation, progression and metastatic dissemination in the context of the ECM and illustrate how dynamic ECM remodelling contributes to all of these stages. We discuss how improving our understanding of ECM remodelling in all stages of carcinogenesis is crucial for uncovering novel therapeutic targets and treatment strategies for a disease which currently presents challenging obstacles with respect to clinical treatment.