Radiation-induced heart disease (RIHD) is the potentially lethal side effect of radiation therapy. Clinical trials and epidemiologic studies show the adverse impact of RIHD on the outcome of long-term cancer survivors. However, what factors affect RIHD and how RIHD develop are not yet clear. On the other hand, as we all known, angiotensin II (Ang II) and aldosterone play a vital pathophysiological role in the common cardiovascular disease, including hypertension, atherosclerosis, heart failure, myocardial infarction and cardiac hypertrophy. The pathophysiology of these various syndromes is similar, starting by prior microvascular injury that leads to subsequent myocardium ischemia, all of which cause late fibrous scars. So the pathophysiology of RIHD is similar to the common heart diseases induced by angiotensin-aldosterone. But the effect of angiotensin-aldosterone on RIHD has little been studied. Thus, in the present hypothesis we suggest that angiotensin II-aldosterone plays an important pathophysical role in RIHD, which was confirmed by our pilot study.