The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guideline advocated several changes from the previous Adult Treatment Panel III guidelines. Assuming full implementation, the 2013 ACC/AHA guideline would identify ≈13 million Americans as newly eligible for consideration of statin therapy. Three features of the 2013 ACC/AHA guideline primarily responsible for these differences are the specific risk assessment tool endorsed, the risk threshold considered sufficient to warrant primary prevention statin therapy, and the decision not to include cholesterol treatment targets. There is no consensus among international guidelines on the optimal approach to these 3 components. The 2013 ACC/AHA guideline recommends assessing absolute risk with the Pooled Cohort equations, which were developed to improve on previous risk assessment models by including stroke as an outcome and by broadening racial and geographic diversity. Each of the leading international guidelines recommends a different equation for absolute risk assessment. The 2013 ACC/AHA guideline advises consideration of statin therapy for an estimated 10-year risk of atherosclerotic vascular disease of ≥7.5%, which is lower than the thresholds recommended by other leading international guidelines. Lastly, the 2013 ACC/AHA guideline does not endorse a treat-to-target strategy but instead specifies the appropriate intensity of statin for each risk category. This approach is shared by the National Institute for Health and Care Excellence guidelines but differs from other international guidelines. In this review, we summarize the 2013 ACC/AHA cholesterol guideline recommendations and compare them with recommendations from Adult Treatment Panel III and other leading international guidelines.