Emerging and low-carbon technologies and innovations are driving a need for domestic sources, sustainable use, and availability of critical minerals (CMs)—those vital to the national and economic security of the United States. Understanding the known and potential health effects of exposures to such mineral commodities can inform prudent and environmentally responsible handling and harvesting. We review the occurrence, use, predominant exposure pathways, and adverse outcome pathways (AOP) for human and fish receptors of those CMs that are nutritionally essential trace metals (specifically, cobalt, chromium, manganese, nickel, and zinc), as well as the rare earth elements. Biological responses to some elements having comparable biogeochemistry can sometimes be similar. Candidate quantifiable biomarkers for assessing potential AOP are conveyed.