Abstract Lead (Pb) isotope compositions of sulfide minerals coupled with rocks associated with an ore deposit provide critical constraints on the source of metals and fluid pathways in a fossil hydrothermal system (Heyl et al., 1966; Stacey et al., 1968; Gulson, 1986; Sanford, 1992). Lead isotope compositions of sulfide minerals also provide chronologic information, either absolute or relative, for ore deposition (for example, Carr et al., 1995) and can also be used as an exploration tool during prospect evaluation (Gulson, 1986; Young, 1995). These varied applications of Pb isotopes to achieve an understanding of the ore genesis process are too diverse to be adequately discussed in a single overview chapter. Instead, this chapter focuses attention on what Pb isotopes tell us about (1) the sources of Pb and other metals in ore deposits, (2) the interaction between hydrothermal fluids and wall rocks, (3) the influence of basement rocks and tectonic setting on Pb sources in ore deposits in magmatic arcs, and (4) the application of crustal-scale Pb isotope variations to an understanding of regional controls on ore deposition. Before Pb isotopes pertinent to understanding ore genesis can be examined, we must review some basic principles of Pb isotope geochemistry (Fig. 1). Elegant discussions of U-Th-Pb geochemistry are presented by Doe (1970), Faure (1977), Zartman and Haines (1988), Gariépy and Dupré (1991), and Dickin (1995). The following discussion is simplified from these sources. Three isotopes, 208Pb, 207Pb, and 206Pb, are partly the radiogenic daughter products from the radioactive decay of one isotope of thorium