Although the proper assessment of the biocompatibility of metallic implant materials often requires a complex consideration of material properties, design-, manufacturing-, and patient-related issues, there are some fundamental principles of physical chemistry and electrochemistry which can be used effectively to point out highly desirable performance characteristics to optimize biocompatibility. The first is the chemical nature of the metal — whether or not it is an essential or nonessential element in the human body. This feature is closely related to the solubility of certain corrosion products, and — in this way — to the availability of the metallic ions for biologically significant reactions. The second major feature is the electrochemical behavior of the metal, including the type of the electrochemical reactions — corrosion and electron exchange -, as well as the mechanism and kinetics of the repassivation of the reactive bare metal (alloy) surface if mechanical breakdown of passivity occurs. In this respect, the most important properties are closely related to the practical nobility — including immunity and passivity — of the metallic system thermodynamically, and to the rate of electrode reactions kinetically. On the basis of these chemical and electrochemical considerations, the unique ability of a selected group of metals to present the least biological effect can be identified. Specifically, titanium, niobium, zirconium, and tantalum are nonessential elements with minimum biological availability and electrocatalytic activity due to their passive oxide layers with extremely low solubility and high protective ability. As exemplified by results of electrochemical and biocompatibility studies of a new titanium alloy, Ti-13Nb-13Zr, the incorporation of Nb and Zr as the only alloying elements in Ti alloys can also be quite beneficial. Additionally, surface oxidation to produce a relatively thick oxide layer may further improve these properties as well as the fretting corrosion resistance.