Cell–substrate surface interaction is highly relevant whether devices are employed as implantables or used in in vitro studies of cells and neurons. The chapter starts with some key facts for non‐biologists before examining the role of surfaces in the adhesion, proliferation, growth and guidance of cells on substrates of various kinds. Electrostatic interaction of polypeptide coatings such as polylysine has been used to ‘graft’ the molecule onto a variety of inorganic and organic substrates. Attempts have been made to combine polylysine with hydrogels and other polymers to produce a three‐dimensional ‘scaffold’ for cell adhesion. Most work on the proteins of the extracellular matrix has centered on laminin, collagen and fibronectin. Extensive studies of the surface morphology of substrates using endothelial, smooth muscle and fibroblast cells, among many, have demonstrated the importance of the part played by surface chemistry in addition to morphology in the biocompatibility of implantable devices and bypass circuitry. The chapter concludes by discussing the interaction between blood and the surface of foreign materials.