The adhesion of cells on an extracellular matrix (ECM) (in vivo) or the surfaces of materials (in vitro) is a prerequisite for most cells to survive. The rapid growth of nano/microfabrication and biomaterial technologies has provided new materials with excellent surfaces with specific, desirable biological interactions with their surroundings. On one hand, the chemical and physical properties of material surfaces exert an extensive influence on cell adhesion, proliferation, migration, and differentiation. On the other hand, material surfaces are useful for fundamental cell biology research and tissue engineering. In this Review, an overview will be given of the chemical and physical properties of newly developed material surfaces and their biological effects, as well as soft lithographic techniques and their applications in cell biology research. Recent advances in the manipulation of cell adhesion by the combination of surface chemistry and soft lithography will also be highlighted.