Guideline panelists must recognize, with humility, the challenges they face in working often without access to informed patient preferences and acknowledge that their recommendations should rarely assume uniform patient values and contexts in favor of a particular course of action. Guideline panels, therefore, should rarely formulate strong recommendations. Panels should become much more comfortable with ambiguity, both in the tradeoffs involved and in the recommendations given, and explicitly report how patient preferences and context were considered in formulating the panels’ recommendations. Clinicians need guidance and clear guidance helps and supports efficient practices. Yet, panels must be wise in recognizing when this expediency is appropriate for patient care and when it hinders patient-centered care. Clinicians should remember that taking care of patients is supposed to be difficult. Although guidelines may simplify this task, when patient preferences and context matter, guidelines must not replace clinicians’ compassionate and mindful engagement of the patient in making decisions together. This is the optimal practice of evidence-based medicine.