Mismanagement of mine waste rock can mobilize acidity, metal (loid)s, and other contaminants, and thereby negatively affect downstream environments. Hence, strategic long-term planning is required to prevent and mitigate deleterious environmental impacts. Technical frameworks to support waste-rock management have existed for decades and typically combine static and kinetic testing, field-scale experiments, and sometimes reactive-transport models. Yet, the design and implementation of robust long-term solutions remains challenging to date, due to site-specificity in the generated waste rock and local weathering conditions, physicochemical heterogeneity in large-scale systems, and the intricate coupling between chemical kinetics and mass- and heat-transfer processes. This work reviews recent advances in our understanding of the hydrogeochemical behavior of mine waste rock, including improved laboratory testing procedures, innovative analytical techniques, multi-scale field investigations, and reactive-transport modeling. Remaining knowledge-gaps pertaining to the processes involved in mine waste weathering and their parameterization are identified. Practical and sustainable waste-rock management decisions can to a large extent be informed by evidence-based simplification of complex waste-rock systems and through targeted quantification of a limited number of physicochemical parameters. Future research on the key (bio)geochemical processes and transport dynamics in waste-rock piles is essential to further optimize management and minimize potential negative environmental impacts.