This review has as its underlying premise the need to become proficient in delivering a suite of element or metal products from polymetallic ores to avoid the predicted exhaustion of key metals in demand in technological societies. Many technologies, proven or still to be developed, will assist in meeting the demands of the next generation for trace and rare metals, potentially including the broader application of biohydrometallurgy for the extraction of multiple metals from low-grade and complex ores. Developed biotechnologies that could be applied are briefly reviewed and some of the difficulties to be overcome highlighted. Examples of the bioleaching of polymetallic mineral resources using different combinations of those technologies are described for polymetallic sulfide concentrates, low-grade sulfide and oxidised ores. Three areas for further research are: (i) the development of sophisticated continuous vat bioreactors with additional controls; (ii) in situ and in stope bioleaching and the need to solve problems associated with microbial activity in that scenario; and (iii) the exploitation of sulfur-oxidising microorganisms that, under specific anaerobic leaching conditions, reduce and solubilise refractory iron(III) or manganese(IV) compounds containing multiple elements. Finally, with the successful applications of stirred tank bioleaching to a polymetallic tailings dump and heap bioleaching to a polymetallic black schist ore, there is no reason why those proven technologies should not be more widely applied.