Guidelines are increasing in importance as healthcare becomes standardized. This article examines the processes by which the new US American College of Cardiology-American Heart Association and UK National Institute of Health and Care Excellence lipid guidelines came to their conclusions and how the nature of the evidence base and health economics contributed to the recommendations made. The writing of guidelines is becoming a systematic formal process with increasing emphasis on maintaining integrity, minimizing conflicts of interest and using consistent systematic methods to define the evidence base, grade its quality and then make recommendations. These processes are illustrated by showing why new cardiovascular disease risk assessment tools were required, what recommendations could be made about diet and lifestyle, why a fixed-dose drug treatment protocol as opposed to a target-based approach was recommended for the management of patients in secondary prevention, diabetes and primary prevention and how these would impact clinical practice. Modern systematic evidence assessment and economic appraisal convincingly favour the use of lipid-lowering drugs especially statins at higher doses than currently prescribed in secondary prevention and at lower risk thresholds in primary care than previously imagined. As long-term adherence to treatment is required patient choice is key to realizing the benefits of these interventions.