Radiation therapy (RT) is a common adjunct therapy in oncology. However, it carries a significant risk of lymphedema when utilized in some anatomic locations. Recent studies have provided insight into lymphedema pathophysiology, diagnostic techniques, and RT. This review will examine the role of RT in upper and lower extremity lymphedema. Radiation’s role in increasing the risk of lymphedema through decreased lymphatic proliferation potential, interstitial fibrosis compressing lymphatic vessels, and mechanical insufficiency of the lymphatic system will be reviewed.