Given Dupuytren’s disease is a hyperproliferative disorder of the palmar fascia without a known cure, radiation therapy in its early proliferative phase with external beam intermediate doses of 21–30 Gy delivered in 7–10 fractions of 3 Gy has generated significant intrigue from patients and clinicians alike with the possibility of a preventative treatment option. With disease progression and transition from hyperproliferation to contracture of palmar nodules, the tissues become avascular and acellular, resulting in less effect from irradiation. This pathologic explanation for the effect of radiotherapy on Dupuytren’s disease is also borne out by the clinical literature, albeit limited, given studies on this topic are heterogeneous and mostly comprised of retrospective case series most commonly originating from Germany. Acute and long-term side effects of radiotherapy in Dupuytren’s disease are generally mild, most often manifesting as erythema, dryness, and desquamation of the skin. The risk of cancer after radiation, a major concern limiting the widespread use of radiation therapy in benign diseases, is estimated to be approximately 0.02–1%, although no cases are currently reported. In summary, evidence to support radiation therapy efficacy in early disease progression without adverse or dangerous side effects remains unclear.