Mine waste rock and drainage pose lasting environmental, social, and economic threats to the mining industry, regulatory agencies, and society as a whole. Mine drainage can be alkaline, neutral, moderately or extremely acidic and contains significant levels of sulfate, dissolved iron, and frequently a variety of heavy metals and metalloids, such as cadmium, lead, arsenic, and selenium. In acid neutralization by carbonate and silicate minerals, a range of secondary minerals can form and possibly scavenge these potentially harmful elements. Apart from the extensively-studied microbial-facilitated sulfide oxidation, the diverse microbial communities present in mine rock and drainage may also participate in the formation, dissolution, and transformation of secondary minerals influencing the mobilization of these metals and metalloids. This article reviews major microbial-mediated geochemical processes occurring in mine rock piles that affect drainage chemistry, with a focus on the role of microorganisms in the formation, dissolution and transformation of secondary minerals. Understanding this is crucial for developing biologically-based measures to deal with contaminant release at the source, i.e., source control.