Ready access to mineral resources is essential for economies and societies worldwide. However, the potential for environmental, ecological, and health impacts from mineral resource development continues to pose substantial technical, regulatory, and societal challenges. Transdisciplinary collaborations between earth, biological, ecological, engineering, health, and social sciences are essential to meet these challenges. The collective work of many geoscientists over the last several decades has demonstrated the foundational role that geoscience plays in this transdisciplinary approach, bringing crucial insights into the influences of ore deposit geology, watershed characteristics, surface- and ground-water hydrology, geochemical processes, and many other factors. Such insights are needed to 1) fully understand pre-mining environmental, ecological, and human health baseline conditions and help establish appropriate post-mining restoration standards, 2) anticipate potential adverse environmental or health impacts and prevent them before they occur, 3) assess, prioritize, and remediate impacts of historical abandoned mining and processing operations, and 4) better communicate potential environmental and health risks posed by mineral deposits and mineral resource development. It important to recognize that assessing potential implications of mineral resource development for environmental quality, ecological health, and human health must be considered together as part of a holistic approach—as one example, natural pre-mining weathering that helps mitigate potential for generation of acid-mine drainage from some lead-rich ore deposits can in turn create highly bioaccessible lead carbonates that greatly enhance the risk for lead poisoning in humans and other terrestrial or aquatic organisms exposed to soils or solid mining/processing wastes. Science-based communication of actual versus perceived risks to populations in areas of past, current, or future mining activity is one example of needed geoscience input into debates surrounding mineral resources, the environment, and health.