In this chapter, a second biosensor technique is described: the quartz crystal microbalance (QCM). The quartz crystal microbalance is a physical technique that detects changes in the resonance frequency of an electrically driven quartz crystal with changes in mass. Unlike surface plasmon resonance (SPR), QCM is affected by both the water that may be associated with the adsorbed layer and by conformational changes in the adsorbed species, while SPR is insensitive to both effects. Thus QCM can both corroborate the findings of an SPR experiment and provide some complementary information. Also, the QCM surface is highly versatile and can range from plain quartz, through gold and other metal surfaces (e.g., titanium or stainless steel) to polymeric materials. Thus, the QCM technique has wide utility in tracking interactions with a variety of materials.