The interactions between cells and their surroundings provide the basis for the coordinated functions of tissues. To understand and control these interactions, we have developed several microfabrication-based approaches to provide model environments for cells. We will describe these approaches, and how they are beginning to elucidate how cells probe and make sense of their environment through biochemical and mechanical means. Integrating microfabricated devices and cells will pave the way for a new era in biomedical research and medicine.