Radiation therapy (RT) plays a prominent role in the treatment of many cancers. With increasing use of RT and high overall survival rates, the risks associated with RT must be carefully considered. Of these risks, the cardiovascular and autonomic toxicities have been of significant concern. In fact, cardiovascular disease is the leading cause of nonmalignancy-related death in cancer survivors. The manifestations of radiation induced cardiac injury include the acute toxicities of myopericarditis and late toxicities including constrictive pericarditis, restrictive cardiomyopathy, coronary artery disease, valvular heart disease, heart failure, and conduction abnormalities. Neck and cranial RT have also been associated with significant long-term toxicities including accelerated occlusive carotid artery disease, autonomic dysfunction due to baroreceptor damage, and development of metabolic syndromes due to damage to the hypothalamic-pituitary axis. The clinical manifestations of radiation induced disease may not present until several years following the delivery of radiation. We review the adverse effects of RT on these organ systems and discuss risk reduction strategies that may effectively mitigate some of these adverse outcomes.