This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the "treat-to-target" paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and "real-world" populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.