The 2013 American College of Cardiology/American Heart Association guidelines for management of low-density lipoprotein cholesterol (LDL-C) to reduce atherosclerotic cardiovascular disease (ASCVD) risk identified four groups of adults (40-75 years of age) with significant evidence for benefit from statin therapy: presence of clinical ASCVD or diabetes, age ≥21 years and LDL-C >190 mg/dl, and 10-year risk of hard ASCVD events ≥7.5 % as determined by the new Cardiovascular Risk Calculator. However, clinicians are faced daily with at-risk patients who do not clearly match one of these statin-benefit groups. Understanding the limitations of available evidence and awareness of additional published guidelines for statin non-benefit groups will help practitioners make personalized decisions with patients and inform the clinician-patient discussion regarding potential risks and benefits of statin therapy.