Data from randomized clinical trials have become the foundation for clinical practice guidelines, including recommendation statements from the US Preventive Services Task Force (USPSTF) on statin therapy for primary prevention.1,2 As new trial data have become available, treatment recommendations have evolved to incorporate these new insights. Yet randomized clinical trials can neither represent the full spectrum of patients nor evaluate all questions and decisions faced in clinical practice. Guideline writers must therefore decide whether and how to generalize from incomplete evidence to care recommendations. Two hypothetical patient scenarios illustrate how far statin therapy guidelines have come and what important gaps remain.