In this era of potent medications and interventional cardiovascular (CV) procedures, the importance of beginning with and including therapeutic lifestyle change (TLC) is frequently forgotten. A major goal of this review article is to show and emphasize that modification of CV risk with nonmedication approaches makes an essential contribution to CV risk reduction. Available information on TLC and modifiable CV risk factors was reviewed and assessed. Modifiable major CV risk factors include diabetes mellitus, hypertension, hyperlipidemia, tobacco abuse, obesity, stress, and sedentary lifestyle. Age as a major CV risk factor is, of course, not susceptible to modification. A contribution to the control of CV risk factors can occur without the start of medications and there is proof of benefit for beginning with a nonpharmacological approach. TLC can benefit all of the major modifiable CV risk factors and there is good evidence for the additional benefit of supervised and group TLC. TLC includes physical activity, diet, and smoking cessation. Evidence for the benefit of TLC in reducing CV disease events is well established. However, medications must be added in those patients with higher CV risk to obtain maximum cholesterol reduction (lower is better for the low-density lipoprotein cholesterol) and good blood pressure control. The benefit of TLC is frequently forgotten in this era of potent medications and invasive procedures. The benefits of diet and physical activity are emphasized with supporting data. Many motivated patients can prolong their lives significantly by dedication to TLC. •Therapeutic lifestyle change (TLC) especially encompasses increased physical activity, healthy diet, and smoking cessation. •There is extensive proof for the benefit of TLC in contributing to cardiovascular (CV) disease prevention. •CV disease has strong metabolic and inflammatory components, both of which can be improved by TLC.