A great deal of consideration has been given in recent years to the biological uses of micro-electro-mechanical systems (MEMS). However, such devices are not yet found in many clinical settings due to lack of appropriate interfacing between these devices and the biological world. This talk will describe approaches to engineer interfaces that enhance the biocompatibility and functionality of implantable MEMS based devices. First, the surface modification of silicon-based devices on the nanometer and micron scale to ensure device functionality and integration will be described. Such chemical modifications must be incorporated onto silicon substrates to modulate the interfacial response, while at the same time ensuring compatibility with microfabrication and micromachining processing. Secondly, microfabrication techniques that can be used to selectively attach and spatially localize chemical species in order to control interfacial reactions with the body will be discussed. By integrating surface modification protocols with MEMS processing, one can create device surfaces that interact appropriately with multiple populations of cells and the surrounding tissue. The identification of principles for engineering microdevice surfaces will aid in developing therapeutic bioMEMS, lab on a chip platforms, and drug delivery systems that can more effectively interface with the biological world.