Colorectal cancer (CRC) remains one of the most common cancers worldwide. Metastatic disease is ultimately fatal when incurable. Cancer research has evolved to take the importance of the tumour microenvironment (TME) into account. The extracellular matrix (ECM) has been viewed merely as a structural scaffold, but it is now evident that the ECM is a highly active part of the TME and affects tumour cell behaviour and metastatic capability. The ECM context and composition are linked to patient outcome and the response to surgical and oncological therapy in CRC patients and may be an area for developing novel biomarkers and targeted therapy. In this review we focus on the components of the ECM in human primary and metastatic CRC. We discuss future aspects of the ECM for targeted therapy, as a source of novel biomarkers, current knowledge of the area and important considerations when studying the ECM in human CRC.