A multifaceted approach incorporating both population-level and targeted individual interventions is required to substantially reduce the burden of atherosclerotic cardiovascular disease globally. Strategies such as legislated salt reduction, public health education campaigns promoting lifestyle changes, and pharmacotherapy for those at highest risk of events are all highly cost-effective and can significantly decrease mortality and morbidity. Targeting statin therapy at those with a 10-year risk of cardiovascular events greater than 20% is projected to avert over 60 million disability-adjusted life years lost over the lifetimes of currently living individuals. Similarly, population-level approaches like salt reduction have the potential to prevent 21 million disability-adjusted life years lost annually. Together, it is estimated these two strategies could cut cardiovascular events in half worldwide. The decision to initiate pharmacotherapy is complex and must account for a patient's absolute risk, the potential benefits of treatment, adverse effects, costs, and patient preferences. No single threshold is appropriate for all patients. Younger individuals with few risk factors and long life expectancies have more to gain from long-term treatment but also potentially more time to experience side effects. Older adults or those with multiple comorbidities may benefit less from lifelong medication but be at higher short-term risk. Shared decision making between clinicians and patients is essential. To translate risk to treatment in a meaningful way, clinicians must understand how to assess risk accurately using tools validated for their patient populations. They need to interpret the risk scores in the context of the best available evidence regarding treatment benefits for different risk strata. They must also explain absolute and relative risks to patients in an understandable fashion, disclosing the uncertainty inherent in any risk prediction model. With this approach, the decision to initiate preventive pharmacotherapy can be tailored to individual patients in a patient-centered manner.