The extracellular matrix (ECM) provides structural and mechanical support for cells as well as delivering them with necessary biochemical cues for development, homeostasis and regeneration of tissues and organs. Medical treatment to repair defects of tissues due to trauma, disease, surgical resection and aging is often based on use of implants made of synthetic biomaterials like ceramics, metals and polymers lacking any biospecific cues that may result in complications such as poor integration, infection or immune rejection. Hence, surface modification techniques have been developed to overcome such complications. In this regard, the layer-by-layer (LbL) technique shows promising results when it is used to mimic several ECM properties by application of matrix components such as polysaccharides and proteins, but also tailoring mechanical properties of such implant coatings. This chapter summarizes the properties of the ECM and their interaction with cells, provides a brief survey on biomaterial-related problems of implantation and several approaches to modify surfaces. We also describe the basis of the LbL technique and provide several examples on its application to modify implant materials including the use of components of the ECM.