Proteins are abundant in biological fluids, readily adsorb to most devices that contact such fluids, and often adversely affect the performance of the device. For example, adsorbed proteins are believed to lower the biocompatibility of implants in the body, non-specific adsorption of antibodies interferes in many solid phase immunoassays, and protein adsorption to the walls of microfluidic devices can cause analyte loss and/or reductions in separation efficiency. In this presentation, I will first give a series of examples illustrating the role of adsorbed proteins in device related problems. A brief review of the major mechanisms of protein adsorption affecting device performance will be given, namely variations in affinity of proteins for surfaces and differences in the ability of adsorbed cell adhesion proteins to support cell adhesion ("molecular potency"). Alterations in molecular potency have often been ascribed to denaturation of adsorbed proteins. However, studies from Norde's lab have shown that adsorbed proteins that exhibit no thermal unfolding enthalpy, and thus appear to be completely denatured, actually retain considerable structure, so these important findings will be presented. In many situations, reducing cell adhesion to a surface is desirable, but ways to accomplish this are not always clear. Towards that end, studies in my lab of platelet and monocyte adhesion to adsorbed fibrinogen have suggested biomaterial design criteria to reduce cell adhesion that are based on the concepts of reducing molecular potency or affinity. Adsorbed proteins sometimes have low molecular potency, but the properties of the surface which cause it are unclear, so it is currently difficult to apply this criteria in designing new surfaces. In contrast, the other design criteria, a need for ultralow fibrinogen affinity surfaces, has been used to make better surfaces, as will be illustrated with glow discharge deposited tetraglyme, and with polyurethanes with added PEO.