The development of biomaterials for drug delivery, tissue engineering and medical diagnostics has traditionally been based on new chemistries. However, there is growing recognition that the physical as well as the chemical properties of materials can regulate biological responses. Here, we review this transition with regard to selected physical properties including size, shape, mechanical properties, surface texture and compartmentalization. In each case, we present examples demonstrating the significance of these properties in biology. We also discuss synthesis methods and biological applications for designer biomaterials, which offer unique physical properties.