The following case studies demonstrate the gap between company-first ESG advocacy and portfolio-first system stewardship for investors concerned about the harmful impacts of climate change and antimicrobial resistance. We show that measuring financial success on an enterprise-by-enterprise basis will never motivate companies or asset managers to transition to safe greenhouse gas emission and antimicrobial use budgets. Instead, the case studies describe how investors can and should use “guardrails” to hold companies and their executives accountable for their full carbon and antimicrobials footprints, even if doing so reduces enterprise value. Only this approach can preserve the long-term value of the diversified portfolios held by pension funds, foundations, endowments, and other institutions working on behalf of everyday savers.