New research shows that enzalutamide radiosensitizes both androgen-dependent and androgen-independent prostate cancer. In vitro, treatment with enzalutamide radiosensitized 22Rv1 and DU145 cells, causing decreased colony survival on irradiation. Enzalutamide plus radiation caused an increase in phosphorylated S1981 ATM and radiation-induced γH2AX and 53BP1 foci, suggesting enzalutamide inhibits repair of radiation-induced DNA double-strand breaks. In vivo, enzalutamide treatment plus irradiation caused a decrease in the size of LNCaP-derived xenograft tumours. In a castration-resistant prostate cancer model, enzalutamide plus radiation significantly reduced tumour progression. Enzalutamide plus radiation also inhibited proliferation in a patient-derived xenograft model of prostate cancer. These results suggest that the efficacy of prostate cancer treatment could be enhanced by concurrent administration of enzalutamide and radiotherapy.