Clastic-dominated lead–zinc (CD Pb–Zn) deposits are an important source of the world’s Pb and Zn supply. Their genesis is contentious due to uncertainties regarding the time of ore formation relative to the deposition of the fine-grained carbonaceous strata that host CD Pb–Zn mineralization. Sulfur-isotopic studies are playing an important role in determining if ore minerals precipitated when hydrothermal fluids exhaled into the water column from which the host strata were being deposited, or when hydrothermal fluids entered the host strata during diagenesis or even later after lithification. Older conventional S-isotopic studies, based on analyses of bulk mineral-separate samples obtained by either physical or chemical separation methods, provided data that has been widely used to support a syngenetic-exhalative origin for CD Pb–Zn mineralization. However, with the advent in the late 1980’s of in situ S-isotopic studies using micro-analytical methods, it soon became apparent that detailed S-isotopic variations of genetic importance are blurred in conventional analytical data sets because of averaging during sample preparation. Clastic-dominated Pb–Zn mineralization in the North Australian Proterozoic metallogenic province and the North American Paleozoic Cordilleran province has been the subject of many stable isotope studies based on both bulk and in situ analytical methods. Together with detailed mineral texture observations, the studies have revealed a similar sulfide mineral paragenesis in both provinces. The earliest sulfide phase in the paragenesis is fine-grained pyrite that sometimes has a framboidal texture. This pyrite typically has a wide range of δ34S values that are more than 15‰ lower than the value of coeval seawater sulfate. These features are typical of, and very strong evidence for, pyrite formation by bacterial sulfate reduction (BSR) either syngenetically in an anoxic water column or during early diagenesis in anoxic muds. The formation of this early pyrite is followed by one or more later generations of pyrite that often occur as overgrowths around the early pyrite generation. The later pyrite generations have δ34S values that are much higher than the early pyrite, often approaching the value of coeval seawater sulfate. Later pyrite formation has been variously attributed to BSR in a more restricted diagenetic environment, to sulfate driven-anaerobic oxidation of methane (SD-AOM) and to abiotic thermal sulfate reduction (TSR), with all three mechanisms again involving coeval seawater sulfate. The main sulfide ore minerals, galena and sphalerite, either overlap with or postdate later pyrite generations and are most often attributed to TSR of seawater sulfate. However, in comparison with pyrite, there is a dearth of in situ δ34S data for galena and sphalerite that needs to be rectified to better understand ore forming processes. Importantly, the available data do not support a simple sedimentary-exhalative model for the formation of all but part of one of the Northern American and Australian deposits. The exception is the giant Red Dog deposit group in Alaska where various lines of evidence, including stable isotopic data, indicate that ore formation was protracted, ranging from early syn-sedimentary to early diagenetic sulfide formation through to late sulfide deposition in veins and breccias. The Red Dog deposits are the only example with early sphalerite with extremely low negative δ34S values typical of a BSR-driven precipitation mechanism. By contrast, later stages of pyrite, sphalerite and galena have higher positive δ34S values indicative of a TSR-driven precipitation mechanism. In CD Pb–Zn deposits in carbonate-bearing strata, carbon and oxygen isotope studies of the carbonates provide evidence that the dominant carbonate species in the ore-forming hydrothermal fluids was H2CO3, and that the fluids were initially warm (≥ 150 °C) and neutral to acid. The δ18O values of the hydrothermal fluids are ≥ 6‰, suggesting these fluids were basinal fluids that evolved through exchange with the basinal sedimentary rocks. Known CD Pb–Zn deposits all occur at or near current land surfaces and their discovery involved traditional prospecting, geophysical and geochemical exploration techniques. Light stable isotopes are unlikely to play a significant role in the future search for new CD Pb–Zn deposits deep beneath current land surfaces, but are likely to prove useful in identifying ore-forming hydrothermal fluid pathways in buried CD Pb–Zn systems and be a vector to new mineralization.