The US Preventive Services Task Force (USPSTF) guideline on statin use for the primary prevention of cardiovascular disease (CVD) in adults and the evidence report that supports the USPSTF statement1,2 published in this issue of JAMA add to 4 other major guidelines on the use of statins published since 2013.3-6 It is self-evident that if they were identical, there would be no justification for more than a single guideline. Therefore, it is important to understand the differences and determine how to provide clinical care and guidance for patients that accounts for the differences. Despite numerous randomized clinical trials (RCTs), important evidence gaps persist, resulting in disparate recommendations among guideline writing groups.