Abstract Bioleaching offers a low-input method of extracting valuable metals from sulfide minerals, which works by exploiting the sulfur and iron metabolisms of microorganisms to break down the ore. Bioleaching microbes generate energy by oxidising iron and/or sulfur, consequently generating oxidants that attack sulfide mineral surfaces, releasing target metals. As sulfuric acid is generated during the process, bioleaching organisms are typically acidophiles, and indeed the technique is based on natural processes that occur at acid mine drainage sites. While the overall concept of bioleaching appears straightforward, a series of enzymes is required to mediate the complex sulfur oxidation process. This review explores the mechanisms underlying bioleaching, summarising current knowledge on the enzymes driving microbial sulfur and iron oxidation in acidophiles. Up-to-date models are provided of the two mineral-defined pathways of sulfide mineral bioleaching: the thiosulfate and the polysulfide pathway.