The ever-increasing rates of obesity and diabetes worldwide have the potential to further fuel the epidemic of cardiovascular disease that we are experiencing today. To slow this epidemic successfully, insulin resistance and associated lipid abnormalities that frequently accompany it are key clinical targets. Yet, we are still challenged to reach the mandated clinical goals for lipids that would minimize the development and progression of cardiovascular disease. Adoption of a comprehensive approach by clinicians, in line with recent recommendations for stricter treatment goals for the at-risk patient, is essential to achieving cardiovascular risk reduction. The challenge for clinicians is integrating strategies, approaches and treatments that address the multiple metabolic defects in patients with insulin resistance and dyslipidemia. New perspectives can help effectively meet this ongoing challenge. Emerging evidence suggests that adipose tissue is intimately involved in the inter-relationships between insulin resistance and dyslipidemia. The future probably involves therapeutic strategies that directly target adipose tissue to optimally reduce cardiometabolic risk.