Evidence from noninvasive ultrasound studies of the neonatal aorta and fetal and early childhood postmortem studies indicates that impaired fetal growth, in utero exposure to maternal hypercholesterolemia, and diabetic macrosomia may all be important risk factors for vascular changes consistent with the earliest physical signs of atherosclerosis. Although the exact mechanisms that underlie these associations remain unclear, animal models have suggested that the use of antioxidant, lipid-lowering, and other innovative therapies may counteract the impact of these intrauterine risk factors for cardiovascular disease. This review summarizes the current evidence for intrauterine factors that have a direct impact on atherosclerosis and provides potential treatment and prevention strategies.