Rising use of advance directives has made surrogate decision making both easier and harder. In many cases, these directives help guide decision making for patients who have lost decision-making capacity. In some cases, however, directives may conflict with what physicians or surrogates view as what is in the patient’s best interest. These conflicts can place substantial emotional and moral burdens on physicians and surrogates, and there is little practical guidance for how to address them. We propose a 5-question framework for untangling the conflict between advance directives and best interests of a patient with a surrogate decision maker: (1) Is the clinical situation an emergency? (2) In view of the patient’s values and goals, how likely is it that the benefits of the intervention will outweigh the burdens? (3) How well does the advance directive fit the situation at hand? (4) How much leeway did the patient provide the surrogate for overriding the advance directive? (5) How well does the surrogate represent the patient’s best interests? We use 2 clinical cases with contrasting outcomes to demonstrate how this framework can help resolve common dilemmas.