Atherosclerosis causes nearly 75% of cardiovascular-related deaths and is found in 80% to 90% of adults >/=30 years old in the United States. Successful treatment minimizes lifetime chances of cardiovascular events, morbidity, and mortality. Risk factors for atherosclerosis should be monitored, beginning in childhood, even in asymptomatic patients. Modifiable factors (e.g., blood pressure, smoking, serum lipids) and nonmodifiable factors (e.g., age, family history) are important in the overall assessment. Clinicians and patients can partner to produce an individualized treatment plan by choosing from a variety of standard approaches. In some patients, improved dietary choices, increased exercise, and smoking cessation will reduce risk to an acceptable degree. To lower risk further, lipid-lowering pharmacotherapy and antihypertensive medication may be combined with these lifestyle improvements. For most of these patients, reducing low-density lipoprotein cholesterol is the most important lipid-lowering goal, and it is best achieved with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). Some patients may benefit from adjunctive therapies that have proven effects (e.g., niacin, fibrates, plant stanols/sterols, omega-3 fatty acids). Antihypertensive regimens may involve stepwise adjustments of multiple medications. Good clinical judgment and communication of expectations and goals are critical for effective management of atherosclerosis.