Atherothrombosis is a generalized and diffuse progressive process manifesting in multiple vascular beds leading to acute coronary syndrome (ACS), ischemic stroke, and peripheral arterial disease. The American Heart Association estimates the prevalence of ischemic stroke, coronary heart disease, and peripheral artery disease to be 4.8, 13.2, and 8 million, respectively. According to the World Health Organization, in 2004, atherothrombosis was the leading cause of death worldwide. Twenty-two percent of all deaths are attributed to atherothrombosis, which is greater than the percentage of deaths from AIDS and cancer combined. Data from the Framingham Heart Study has shown atherothrombosis significantly reduces life expectancy. According to current data, there is an established relationship among coronary artery disease, peripheral vascular disease, and cardiovascular disease. The REACH registry demonstrated that the 1-year cardiovascular event rates increase with the number of symptomatic disease locations. Unstable angina/non-ST-segment elevation MI is a major public health problem and represents the most common reason for hospital admission for coronary heart disease. Classification of “vulnerable patients” will help identify those with a high probability of developing cardiac events in the near future, and their early detection and treatment would help 50 to 60 million Americans over the age of 35. The management of patients with ischemic coronary disease consists of 2 approaches: revascularization and systemic (aspirin, clopidogrel, lipid-lowering therapy, angiotensin-converting enzyme inhibitors, and β-blockers). There is a substantial long-term cardiovascular risk after discharge with non-ST-elevation acute coronary syndrome with an annual mortality rate estimated at 6%. This emphasizes the importance of risk stratification and aggressive management strategies that target high-risk patients. Based on CAPRIE study and Cure trial results, patients can benefit from clopidogrel or its combination with aspirin. CRUSADE registry data reveal some acute medications are still being underused, most notably GP IIb/IIIa inhibitors (47%) and clopidogrel (54%). Improved American College of Cardiology/American Heart Association guideline adherence is directly associated with reduced in-hospital mortality, and thus the need for quality improvement is imperative.