Tissue engineering aims to restore normal physiological function of damaged or diseased tissues through a specifically tailored combination of cells, extracellular matrices (ECMs), and mechano-chemical stimuli. Therefore, it is crucial to have a good knowledge of our tissues, which are mainly composed of cells, soluble factors, water and the ECM. This matrix not only provides structural support for our cells in a given tissue, but also provides a rich source of signals for the cells. The first part of this chapter will therefore focus on the main mechanical properties, functions and composition of the ECM in different tissues. The properties of these native ECMs, from composition to architecture, are so relevant that it is common to use these decellularised matrices as scaffolds for various tissue engineering applications. The chapter concludes by highlighting the relevant role of cell-matrix adhesions. Finally, the chapter ends with conclusions and questions to reinforce the different concepts and aspects covered in this chapter.