Mining activities have created great wealth, but they have also produced colossal quantities of tailings. An important source of heavy metal contamination, sulfide tailings are usually disposed of in open-air impoundments and thus are exposed to microbial oxidation. Microbial activities greatly enhance sulfide oxidation and result in the release of heavy metals and the precipitation of iron (oxy)hydroxides and sulfates. These secondary minerals in turn influence the mobility of dissolved metals and play important roles in the natural attenuation of heavy metals. Elucidating the microbe–mineral interactions in tailings will help us mitigate the environmental impacts of mining activities.