This chapter discusses the biocompatibility of dental amalgam, which remains controversial for this widely used restorative material. Information is presented on the description, manipulation, composition, structure, and properties of dental amalgam, and the clinical behavior of dental amalgam restorations. Articles on biocompatibility of dental amalgam restorations are reviewed, notably recent clinical studies. While studies indicate that properly placed restorations present no health hazards, further research is needed to ensure that released mercury does not cause adverse physiological changes. The chapter concludes with guidelines for manipulating dental amalgam to avoid biocompatibility concerns and the current state of research in this field.